Stable compositions of uncomplexed iodine and methods of use

ABSTRACT

The present invention is directed to a composition in solution (often, an aqueous solution) which comprises a combination of molecular iodine (I2) and an acceptable source of iodate (IO3), and an acid (inorganic or organic), wherein iodide and iodate are present in the composition at a molar ratio of about 0.1 to about 25, the concentration of uncomplexed molecular iodine is a disinfectant, biocidal and/or antimicrobial (depending upon the end use of the composition) effective amount the concentration of acid in the composition is effective to provide a buffering pH in the composition ranging from about 1.5 to about 6.5. Compositions according to the present invention are storage stable for unexpectedly long periods of time (up to about 5 years), and find use as disinfecting solutions, as germicides and/or biocides (e.g. antiviral, antibacterial, antifungal, antispore etc.) for various surfaces and solutions including living and inanimate surfaces and are particularly useful because of their low cost, their reduced use of iodine, their activity (because of the high concentration of free molecular iodine in solution), their reduced environmental impact, their long term storage stability and their reduced toxicity. They also have particular utility in treating food surfaces to retard spoilage, increase useful shelf-life and minimize the human and economic cost of food waste. The compositions inactivate viruses, bacteria (both gram negative and positive), spores and fungi. Compositions according to the present invention may be used and stored in a variety of materials, given the substantial absence of corrosion (non-corrosive) these compositions display. Dental compositions (e.g. preprocedure rinses and other compositions) and methods related thereto are also disclosed.

RELATED APPLICATIONS

This application is a divisional application of U.S. application Ser.No. 16/110,902 filed on Oct. 23, 2018, which is a divisional applicationof United States national phase patent application Ser. No. 15/128,556filed on Sep. 23, 2016, which is a United States national phase patentapplication based upon international patent application numberPCT/US2015/022643 filed on 26 Mar. 2015, which claims the benefit ofpriority of U.S. provisional patent application No. 61/972,626 filed onMar. 31, 2014. The entire contents of said applications are herebyincorporated by reference herein.

FIELD OF THE INVENTION

The present invention is directed to compositions which comprise acombination of molecular iodine (I₂) and an acceptable source of iodate(IO₃ ⁻), and an acid (inorganic or organic), wherein the iodate and themolecular iodine are present in the composition at a molar ratio ofabout 0.1 to about 25 to about 1.5 to about 5.0, often about 0.25 toabout 10 to about 1.25 to 5.0, and about 1.0 to 7.5 to about 1.25 to 5.0or about 1.25 to about 5.0 to about 1.5 to about 5.0, the concentrationof uncomplexed molecular iodine is a disinfectant, biocide and/orantimicrobial (depending upon the end use of the composition) effectiveamount ranging from about 0.5 ppm to about 2500 ppm, often about 1 ppmto about 1000 ppm, about 10 μm to about 500 ppm, about 20 ppm to about350 ppm and about 25 ppm to about 300 ppm, about 35 ppm to about 250ppm, about 50 ppm to about 200 ppm, the concentration of acid in thecomposition is effective to provide a buffering pH in the compositionranging from about 1.5 to about 6.5 (often about 2.0 to about 6.5 withinthis range), preferably 2.0 to about 5.5, often about 2.0 to about 5.0).Compositions according to the present invention are storage stable forunexpectedly long periods of time (up to about 5 years, often for atleast about 2-4 weeks, often 1 month or more as described herein), andfind use as disinfectants, sanitizers, sterilants, sporicides. foodspoilage deterrents and biocides that kill viruses, fungi, bacteria,spores, mold and all other known microbes, and are particularly usefulbecause of their low cost, their reduced use of iodine, their activity(because of the high concentration of free molecular iodine insolution), their reduced environmental impact, their long term storagestability and their reduced toxicity. Compositions for treating and/orpreventing viral, bacterial (both gram negative and positive), parasite,fungal and spore-based infections, especially including Norovirus,Poliovirus, Hepatitis A, Klebsiella pneumonie, Staphyloccus aureus,Trichophyton mentagrophytes, Acinetobacter baumanni and Candida albicansin subjects or patients in need and for treating surfaces, includingkeratinous and mucosal tissue surfaces and wounds, represent additionaluses of the present invention. Compositions according to the presentinvention may be used and stored in a variety of embodiments, given thesubstantial absence of corrosion (non-corrosive) these compositionsdisplay.

BACKGROUND OF THE INVENTION

Elemental iodine (I₂) is a blue-black crystal with a high metallicluster that sublimes readily to generate a violet-colored vapor. Insolution, the term “molecular iodine” has been used to refer to the I₂molecule. Molecular iodine (I₂) is a hydrophobic molecule that is highlypolarizable. The chemical reactivity of I₂ includes: addition to doublebonds, oxidization of sulphydral groups, addition to activated aromaticgroups and formation of N-iodo derivatives. However, iodine also reactswith water to form iodine species that exist in several differentoxidation states; molecular iodine is unstable in water due to thesereactions.

The term “iodine” has been, and continues to be used imprecisely inmedical literature to refer to several different chemical entities andcomplicated formulations that contain diverse iodine species. Theimprecise description of iodine compositions in the art may stem, inpart, from ambiguous analytical characterizations. For example,thiosulfate titration is the most commonly used USP method to measure I₂but this method also detects triiodide and hypoiodous acid in additionto molecular iodine (I₂). From this point forward the presentapplication shall use the term “molecular iodine” (I₂) or “uncomplexedmolecular iodine” when referring to the I₂ species in an aqueousenvironment.

In an aqueous environment iodine exists in several forms or species.These species include: iodide (I), molecular iodine (I₂), hypoiodousacid (HOI), iodate (IO₃ ⁻), triiodide (I₃ ⁻) and polyiodides (e.g., I₅ ⁻or I₇ ⁻). These species have different physical and chemical properties.The instability of polyvinylpyrrolidone-iodine (PVP-I) or starch-iodinecompositions is primarily caused by hydration of molecular iodine toform hypoiodous acid which ultimately leads to formation of iodate andloss of iodine atoms from the complex equilibrium that yields a very lowconcentration of uncomplexed molecular iodine. Uncomplexed moleculariodine is responsible for the biocidal activity of iodine germicides.The instability of molecular iodine in an aqueous environment is aprimary formulation constraint that has influenced the development ofall aqueous based iodine germicides that rely upon complexed moleculariodine.

Four basic formulation strategies have been used to overcome aqueous I₂instability. These include: (a) the use of iodide as a complexing agent,(b) the use of organic complexing agents such as polyvinylpyrrolidone,starch and other complexing agents which complex I₂, (c) solidcompositions that release elemental iodine slowly and (d) the use ofoxidation reactions to produce iodine in situ. Each approach hasinherent constraints and potential benefits that need to be evaluated inlight of an intended application. However, adopting a formulationstrategy that requires complexation of molecular iodine i.e., the twostrategies identified as (a) and (b) above, necessarily requireincorporation of considerably more iodine than an approach based onuncomplexed iodine in order to provide a similar biocidal capability.

Formulations based on iodine-complexation require additives that reducethe chemical activity of molecular iodine in a composition via theexpedient of a relatively tight binding between said additive andmolecular iodine. That is, the binding between complexing agent andmolecular iodine must be tight enough to prevent hydration of moleculariodine. This approach results in a very low concentration of free oruncomplexed molecular iodine and a very high concentration of boundmolecular iodine. As an example, commonly used 10% PVP-I typicallydelivers 2-4 ppm of unbound molecular iodine in a composition thatcontains over 15,000 ppm of total iodine atoms. The level of totaliodine is obviously much higher than that amount of pure moleculariodine required for biocidal efficacy. Drawbacks of such compositionsinclude undesirable toxicological properties, unwanted interactions withinanimate materials, increased costs and a higher environmental burden,as well as limited efficacy for many indications due to lowconcentrations of uncomplexed iodine and poor stability upon dilution.

U.S. Pat. No. 5,629,024 describes methods to generate molecular iodinein an aqueous environment, but the compositions described therein do nothave a useful activated use-life because the molecular iodine isdissipated rapidly via reaction with water. Despite the fact that thecompositions described in 5,629,024 patent do not require high levels ofmolecular iodine the patent does require generation of molecular iodineby the peroxysulfate anion at a controlled rate equal to the rate ofloss of molecular iodine. Although this approach is viable, the methoddescribed in 5,629,024 is limited to applications where the loss ofmolecular iodine is equivalent to, or slightly greater than, the minimumgeneration rate of molecular iodine over the intended period of use.Additionally, the method described in 5,629,024 requires users toactivate the composition of interest prior to use since it cannotprovide a stable formulation that can be manufactured and placed intocommercial distribution channels, resulting in unnecessary inconvenienceand chance of operator error.

The use of iodate in iodophor compositions is a well-known formulationapproach to one skilled in the art that is used to increase thestability of molecular iodine in these complex formulations. Winicov andOberlander (U.S. Pat. No. 4,271,149) described methods to stabilizecomplexed iodine compositions via the use of an iodate ion in the rangeof about 0.005% to 0.2% within a pH range of pH 5-7. McKinzie andWinicov (U.S. Pat. No. 5,643,608) developed iodophors with high levelsof molecular iodine using mixtures of iodine-iodide-iodate compositionswith stability for 1 to 3 months which contained 0.005-0.5% iodate byweight in a pH range of about 2.0-4.5. Buxton et. al. (EP0448288 B1)describes the use of iodate in a concentration range of 0.01% to 0.04%in stabilized iodophors to provide reduced irritancy. Khan and Moellmer(U.S. Pat. No. 5,116,623) describe the use of periodate to stabilizeiodophors. All of these patents described iodine formulations whereinthe iodine is complexed and therefore the interaction of iodate in theseiodide rich environments is not precisely controlled or predictable incontrast to the present invention.

The marketplace has shown a long-felt need for a storage stable,non-toxic germicide that can reduce transmission of infectious agentsand inactivate resistant microbial strains. For example, microbialinfections, from viruses, spores, bacteria, fungi, etc., for example,Norovirus infections, which induce stomach pain, nausea, diarrhea andvomiting, place a significant economic and health burden on society.Norovirus and other viruses and bacteria are transmitted by humancontact, contaminated food or water, or by touching contaminatedsurfaces. Proper prevention techniques in the healthcare and foodpreparation workplace require repeated daily hand disinfection which canbe problematic since efficacious hand sanitizers often cause irritationwhen used chronically. The same problem persists in hospitals withrespect to the cause of nosocomial infections and resistantstaphylococcus (MRSA) and streptococcus infections, among numerousothers. A key objective of the formulations contemplated in thisapplication is the rapid elimination (in some cases to unmeasurablenumbers) of viruses, spores, bacteria and fungi such as norovirus andall resistant bacterial microbes, especially including, for example,multiple drug resistant staph infections (MRSA).

The annual economic cost of food spoilage to producers, processors,transporters, retailers and consumers is estimated to be $750 billiondollars globally. Approximately 1.3 billion tons of foods are wastedevery year. This spoilage is primarily caused by the action of microbeson the surfaces of the affected foodstuffs (meats, berries, vegetables,fruits, seafood and grains). The compositions described in thisapplication are suitable to both sanitize and extend the shelf life ofmany foods thereby providing a significant economic benefit.

SUMMARY OF THE INVENTION

The present invention describes compositions that provide formulationsof uncomplexed molecular iodine that are stable, non-irritating,non-toxic and capable of being placed into commercial distributionchannels with extended storage stability (months or years). In oneembodiment, the compositions described in this application: (a) providea constant thiosulfate titratable level of iodine over the shelf-life ofthe product and (b) exhibit a chemical activity of molecular iodine thatis at least about 50% (at least about 55%, at least about 60%, at leastabout 65%, at least about 70%, at least about 75%, at least about 80%,at least about 85%, 90%, 95% or more) of an equivalent concentration ofmolecular iodine (based upon the total atoms of iodine) as measuredpotentiometrically in a 0.1N HCl solution. Thus, the presentcompositions provide an unexpectedly high level of activity of moleculariodine as an uncomplexed species, in a composition which is storagestable.

In other embodiments, the present invention describes compositions thatcontain uncomplexed molecular iodine in combination with complementarygermicides that act to broaden the spectrum of activity and/or speed ofaction of said germicides, sometimes unexpectedly resulting insynergistic activity. Virtually any pathogen which can cause healthproblems can be eliminated from surfaces using compositions according tothe present invention.

In contrast to the prior art, the present application describesgermicidal compositions wherein the majority of molecular iodine isuncomplexed. Formulations based on iodine-complexation require additivesthat reduce the chemical activity of molecular iodine via the tightassociation required to stabilize molecular iodine. This complexationapproach results in a very low chemical activity of free or uncomplexedmolecular iodine and a very high concentration of bound moleculariodine, thus reducing the biocidal activity of the composition as awhole and requiring much higher levels of iodine to provide sufficientmolecular iodine to function effectively. As an example, commonly used10% PVP-I typically delivers 2-4 ppm of unbound molecular iodine in acomposition that contains over 15,000 ppm of total iodine atoms. Thelevel of total iodine is obviously much higher than that amount ofuncomplexed molecular iodine required for biocidal efficacy. Drawbacksof such compositions include undesirable toxicological properties,unwanted interactions with inanimate materials, skin staining, increasedcosts, a higher environmental burden and lower efficacy per unit mass ofiodine.

The present application contemplates a wide range of use applications.The use of uncomplexed iodine is desirable because thedisinfectant/biocidal/antimicrobial activity of a composition can beoptimized for a specific use even if that application requires highlevels of such activity. The use of uncomplexed iodine is beneficial ascompared to iodophors because (a) free, or uncomplexed, molecular iodineis the biocidal agent in all iodine-based germicides including iodophorswhereas complexed iodine per se does not exhibit biocidal activity untilit dissociates from its complexing agent providing free molecular iodineor I₂; (b) the complexing agents used in iodophors can interact withcomplementary biocides that could otherwise be added to an iodine-basedgermicide to increase its level or range of germicidal activity; (c)iodophors are more costly to produce, (d) uncomplexed iodineformulations can achieve higher levels of free molecular iodine withgreater biocidal activity than iodophors, and (e) uncomplexed iodineformulations are substantially less toxic.

In one embodiment, the present invention is directed to a compositioncomprising an effective amount of a source of iodide (often from asoluble iodide salt such as sodium and/or potassium iodide, amongothers) and iodate (often from a soluble iodate salt such as sodiumiodate, potassium iodate, calcium iodate, potassium hydrogen iodate,etc. or mixtures thereof) in solution wherein the molar ratio of iodideto iodate (which forms molecular iodine and therefore serves as a sourceof molecular iodine) is about 0.1 to about 25, often about 0.25 to about10, often about 0.5 to about 7.5, about 1 to about 6.5, about 1 to about5 or about 1.25 to about 5.0 and a predetermined amount of a bufferingacid, wherein the acid is included in said composition in an amountwhich will provide a buffered pH within the range of about 1.5 to about6.5, 1.5 and about 6.5, about 2.0 and about 6.0, about 2.5 to about 5.5,about 2.0 to about 5.0, wherein at least about 50% of the total amountof molecular iodine in the composition is uncomplexed and theconcentration of uncomplexed molecular iodine in the composition rangesfrom about 0.5 ppm to about 2500 ppm, often about 1 ppm to about 1000ppm, about 10 μm to about 500 ppm, about 20 ppm to about 350 ppm andabout 25 ppm to about 300 ppm, about 35 ppm to about 250 ppm, about 50ppm to about 200 ppm. These compositions generate molecule iodine whichprovides the principal antimicrobial activity. Compositions according tothe present invention are capable of disinfecting surfaces, solutions(including water supplies such as swimming pools, municipal drinkingsources, etc.) and/or otherwise eliminating microbes from surfaces towhich the compositions are applied to a level of at least 99%, often atleast 99.9%, often at least 99.99%, often at least 99.999%, often atleast 99.9999%, often at least 99.99999%, and often more than 99.99999%to a level such that the microbes initially in solution or on thesurface treated with compositions according to the present invention arebeyond the capability of contemporary analysis (i.e., they areessentially eliminated from the surface treated with compositionsaccording to the present invention).

Treatment of vegetables, fruits and other foods immediately prior to usepresents a unique use case. In this case the vegetables, fruits or otherfoods may be treated; the iodine-based treatment composition may bediscarded and the foods immediately eaten. The benefit of an extendedshelf-life for the composition is not significant in this use case.Therefore, in this embodiment one preferred method for treatment caninclude in one embodiment, a composition comprising an effective amountof a source of iodide (often from a soluble iodide salt such as sodiumand/or potassium iodide, among others) and iodate (often from a solubleiodate salt such as sodium iodate, potassium iodate, calcium iodate,potassium hydrogen iodate, etc. or mixtures thereof) wherein the molarratio of iodide to iodate (which forms molecular iodine and thereforeservers as a source of molecular iodine) is about 4.0-7.5 to about 1.0,often about 4.5-6.5 to about 1.0 and most often about 5.0 to about 1.0,wherein the acid is included in said composition in an amount which willprovide a buffered pH within the range of about 1.0 and about 6.5,about, 1.5 and about 6.5, about 2.0 and about 6.0, about 2.5 to about5.5, about 2.0 to about 5.0, about 1.0 to about 3.5 to about 4, whereinat least about 80% of the total amount of molecular iodine in thecomposition is uncomplexed and the concentration of uncomplexedmolecular iodine in the composition ranges from about 1 ppm to about 500ppm, about 10 ppm to about 150 ppm, often about 25 ppm to about 200 ppmand about 35 ppm to about 300 ppm. These compositions generate moleculeiodine which provides the principal antimicrobial activity. In certainembodiments for the rapid generation of iodine within a period of nomore than about several minutes (e.g. about 30 seconds to about 15minutes, about 1 minutes to about 10 minutes, about 2 minutes to about7.5 minutes, about 2 minutes to about 5 minutes) for disinfection offoodstuffs such as vegetables and fruits and the like, a preferred lowerpH range of about 1.0 to about 3.5 to 4.0, or about 2.0 to about 4.0 isused along with a preferred molar ratio of iodide/iodate of about 5.0.Compositions according to the present invention are capable ofeliminating microbes from surfaces of food to which the compositions areapplied to a level of at least 99%, often at least 99.9%, often at least99.99%, often at least 99.999%, often at least 99.9999%, often at least99.99999%, and often more than 99.99999% to a level such that themicrobes initially in solution or on the surface treated withcompositions according to the present invention are beyond thecapability of contemporary analysis (i.e., they are essentiallyeliminated from the surface treated with compositions according to thepresent invention). This includes virus such as norovirus.

In other embodiments of the present invention, the present compositionsmay include an effective amount of additional germicidal agents,including a peroxide compound, for example, hydrogen peroxide, or aper-oxygen compound, for example, peracetic acid, or an alcohol, forexample, ethanol.

In certain embodiments, peracetic acid is preferably used in combinationwith the disinfectant compositions of the present invention for surfacedisinfection, especially hard surface disinfection. In theseembodiments, the composition advantageously may employ a dual chamberdispensing system for combining/delivering peracetic acid along with thepresent disinfectant compositions onto a surface to be disinfected.Usable ranges of peracetic acid fall within the overall range of about200 ppm to about 10,000 ppm. By nature, dilute peracetic acid isunstable, but has a useful commercial shelf life. Peracetic acid istypically supplied in concentrations of 5%, 15% and 35.5% solutions,each of which has about a one year shelf life (stability). Once dilutedfor use, these solutions become readily unstable. Some dilute fixedconcentrations can be supplied, e.g. 1400 ppm or other lowerconcentrations, but shelf life of these solutions is questionable. Thus,another embodiment of the present invention is directed to a method todeliver peracetic acid in combination with the present compositions suchthat the peracetic acid solution is diluted only at the time of use.This embodiment comprises a two part container or two containers, thefirst of the two parts or containers comprising the storage stableconcentrated peracetic acid solutions (e.g., a 5% solution) and thesecond of the two parts or containers comprising the compositionaccording to the present invention which are delivered to the surfaceseparately from the two parts or containers. It is noted that peraceticacid and molecular iodine and/or alcohol cannot be safely mixed(potential strong reaction between the peracetic acid and the alcoholand/or iodine) and even if they could, the peracetic acid dilution wouldresult in instability and reduce the shelf life of the composition. Anumber of dispensing systems may be used in this aspect of theinvention. For example, the dispensing system used in this embodimentcomprises an off the shelf dual compartment sprayer which proportionsthe components at the time of delivery from the spray head, oralternatively, the system comprises two bottles with tubing connected totwo separate spray heads or two tubes from two bottles using differentdiameters to meter the liquids both of which are connected to a singlespray head.

In still other embodiments, the present compositions further compriseeffective amounts of additional components selected from non-aqueoussolvents (ethanol, isopropanol, n-propanol, etc.) surfactants,emulsifiers, including secondary emulsifiers, emollients, oils,humectants, oils (polar and non-polar), conditioning agents,thickeners/thickening agents, medicaments, fragrances, preservatives,skin protecting agents, pigments, dyes, coloring agents, gelling agentsand mixtures thereof in order to provide compositions exhibitingcharacteristics consistent with the use of the compositions, dependingupon the surface to be treated, which surfaces include biologicalsurfaces especially including keratinous and mucosal tissue and/orwounds of an animal, including a human.

In other embodiments the composition according to the present inventionis directed to a gel or thickened composition for human and veterinaryuses especially for periodontal uses, i.e., in periodontal applications,especially including the treatment and disinfection of periodontalsurfaces, including before and after oral surgery and the like. In thisembodiment, the gel or thickened composition is placed in contact withperiodontal surfaces by means of a tray, syringe, infusion or similarapproach which exposes the periodontal surface to the composition. Instill other embodiments, a liquid composition is provided as a dentalwash, rinse or irrigant for human and veterinary applications, includingto reduce mouth odor and/or to reduce (knock down) potential bacterialload in the mouth of a subject to whom the rinse is applied. In oneembodiment, the present invention provides an iodine containingmouthwash as a dental preprocedure rinse. This mouthwash isadvantageously used by dental patients prior to any procedure (e.g., atreatment procedure including a surgery, dental cleaning and/orprophylaxis) to reduce or knock down the microbial load to help reducethe likelihood (prevent) disease transmission from the patient to thedental staff, for example, when the microbes become aerosolized due towater spray, air spray, ultrasonic instrumentation or the spray from ahigh speed handpiece utilized in dental procedures. In this embodiment,the concentration of molecular iodine ranges from about 3 to about 350ppm, often about 5 to about 200 ppm, more often about 10 to about 100ppm.

In still other embodiments, a gelled composition is provided which mayfurther include packaging such as in a semi-permeable pouch or otherpackaging to allow delivery of iodine vapor from the compositionenclosed therein at a controlled rate to kill mold and bacteria in afood or other sample, for example, in a container of berries or otherfood item. In this embodiment, for example, a small semi-permeable pouchor other packaging which is adapted to allow the release of iodine vaporfrom the composition could be placed in a container with food items(often fruits and/or vegetables) to be treated, the container beingpreferably sealed to prevent or inhibit the release of iodine vaporduring the treatment of the food items. In this application, the smallpouch or other packaged composition could be placed in the container incontrast to immersing the food items in an aqueous solution of iodine.

In further embodiments, the present invention is directed to methods ofdisinfecting a solution or a surface, including a biological surfacecomprising exposing a solution or surface to be disinfected with aneffective amount of a composition according to the present invention.Methods according to the present invention may be used to disinfectsurfaces, including biological surfaces including hands, and skin areasto be disinfected after a wound to disinfectant the wound, before amedical procedure (e.g. surgery) and other use indications (for example,treatment of hard surfaces on which food is prepared) such that numerousmicrobes are substantially eliminated and/or inhibited from growing onthe exposed surface. Methods of disinfection may be used to disinfectsurfaces from a variety of microbes, including viruses, bacteria, fungi,spores, mold, parasites and prions, among others, as otherwise describedherein.

Definitions

The following terms are used to describe the present invention. Ininstances where a term is left undefined, the term is given its artrecognized meaning. In accordance with the present invention there maybe employed conventional chemical synthetic methods and other biologicaland pharmaceutical techniques within the skill of the art. Suchtechniques are well-known and are otherwise explained fully in theliterature.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise (such as in the case of a groupcontaining a number of carbon atoms in which case each carbon atomnumber falling within the range is provided), between the upper andlower limit of that range and any other stated or intervening value inthat stated range is encompassed within the invention. The upper andlower limits of these smaller ranges may independently be included inthe smaller ranges is also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either bothof those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, the preferredmethods and materials are now described.

It is to be noted that as used herein and in the appended claims, thesingular forms “a,” “and” and “the” include plural references unless thecontext clearly dictates otherwise.

The term “compound”, as used herein, unless otherwise indicated, refersto any specific chemical compound disclosed herein. Within its use incontext, the term generally refers to a single compound as otherwisedescribed herein. Compounds which are disclosed are those which arestable.

The term “patient or subject” is used to describe an animal, including adomesticated animal (such as a domesticated bird, a dog, cat, cow,horse, pig, sheep, goat, fish, etc.) especially including a mammal,especially a human to which compositions according to the presentinvention may be applied.

The term “effective” is used, in context, to describe an amount orconcentration of a compound, composition or component, as otherwisedescribed herein which is included or used to provide an intended effector trait as otherwise described in context, such as disinfection,biocidal and/or antimicrobial activity, or other attribute, such asbuffering effect, depending upon the final composition, or an effect ortrait dependent upon the nature of the final product such assurfactancy, emulsification (emulsifiers), emolliency, wetability, skinadherence, storage stability, and/or solubility to a formulation or toproduce a compound or composition according to the present invention. Itis noted that when the term “effective” is used within the context ofdisinfecting a surface with a composition according to the presentinvention, this term is used to describe an effective amount of thecomposition containing an effective amount of uncomplexed moleculariodine which is contacted with the surface to be disinfected for aperiod of time and at a temperature (often at room temperature, but incertain embodiments at elevated temperatures such as at 37 degrees toabout 50 degrees C. or more, including in certain embodiments withspores and mold, among others) sufficient to disinfect the surface.

The term “source of iodide” is used to describe a compound or materialwhich is generally, an iodide salt, which provides an effectiveconcentration of iodide anion in solution which is used in compositionsaccording to the present invention. The source of iodide used incompositions according to the present invention includes any appropriatesource of iodide, especially iodide salts (and includes hydroiodic acid)which dissociate when placed in solution. Preferred sources of iodidefor use in the present invention include NaI (sodium iodide), KI(potassium iodide), LiI (lithium iodide), CaI₂ (calcium iodide) and MgI₂(magnesium iodide), among others.

The term “source of iodate” is used to describe an appropriate compoundor material (generally, an iodate salt), which provides a concentrationof iodate anion in solution which is used in the present invention. Thesource of iodate used in compositions according to the present inventionincludes any appropriate source of iodate, especially iodate salts whichdissociate when placed in solution. Preferred sources of iodate for usein the present invention include NaIO₃ (sodium iodate), KIO₃ (potassiumiodate), LiIO₃ (lithium iodate), CaIO₃ (calcium iodate) and MgIO₃(magnesium iodate), among others.

The term “disinfect” shall mean eliminating microbes from surfaces towhich the compositions are applied or solutions in which thecompositions are added to a level of at least about 99%, often at leastabout 99.9%, often at least about 99.99%, often at least about 99.999%,often at least about 99.9999%, often at least about 99.99999%, and oftenmore than about 99.999999 (the remaining population of microbes is lessthan about 10⁻⁶), 99.9999999 (the remaining population of microbes isless than about 10⁻⁷) or 99.9999999% (the remaining population ofmicrobes is less than about 10⁻⁸) or even lower, including to a levelsuch that the microbes initially in solution or on the surface treatedwith compositions according to the present invention are eliminated to alevel beyond the capability of contemporary analysis (i.e., they areessentially eliminated from the surface treated with compositionsaccording to the present invention).

The term “surface” shall mean any surface to which compositionsaccording to the present invention are applied. The surface is anysurface for which the present compositions may be used for theirdisinfectant, antimicrobial and/or biocidal activity, for example, anyinanimate surface such as the surface of a floor, countertop, table,furniture, any surface which comes in contact with food or the surfaceof the food itself, medical and/or surgical equipment or a surface or akeratinous surface such as the skin, hair or nails (ungual) or mucosalsurface (including internal surfaces of an animal or human, such as thethroat, mouth (including teeth and/or gums) or nasal passages or othermucosal surfaces in the body including the ears, vagina or internalsurfaces in an animal, including a human) or a wound of a patient orsubject. In certain applications, the compositions may be usedinternally in a patient or subject, for example, pursuant to medicalprocedures. In other applications, the compositions are used todisinfect the hands and/or other body surfaces of a subject or patient,including skin surfaces in which incisions are to be made pursuant tosurgical procedures. In certain important applications associated withfood preparation, compositions according to the present invention areapplied to any surface where food is stored and/or prepared or to thehands or other surfaces of individuals who are engaged in foodpreparation or to the surfaces of the food itself. Other importantapplications include direct application to mucosal and subgingivalsurfaces, ear drops and toothpaste. In addition, it is anticipated thatthe compositions described herein shall be directly applied to mucosalsurfaces, e.g. douche, oral irrigation, lavage, oral ingestion, throatspray or gargle, nasal/sinus spray or mouthwash.

The term “molecular iodine” or “uncomplexed molecular iodine” as usedherein, refers to diatomic iodine, which is a molecule comprised of 2iodine atoms and is represented by the chemical symbol I₂ (CAS RegistryNumber: 7553-56-2). Some of the prior art uses the term “elementaliodine” to describe the same chemical entity.

The term “iodide” or “iodide anion” refers to the anion that isrepresented by the chemical symbol I⁻ (CAS Registry Number: 20461-54-5).For instance, the iodide anion forms when a salt of iodine is dissolvedin water. Suitable counter-ions for the iodide anion include sodium,potassium, calcium, magnesium and the like.

The term “chemical activity” refers to a measure of the effectiveconcentration of molecular iodine when in the presence of other chemicalspecies. The difference between the chemical activity of moleculariodine and the concentration of molecular iodine in iodophors is largelya measure of complexation of molecular iodine in iodophors.

The term “uncomplexed molecular iodine” or “free molecular iodine”refers to molecular iodine which is in free form. In compositionsaccording to the present invention at least about 50% (at least about55%, at least about 60%, at least about 65%, at least about 70%, atleast about 75%, at least about 80%, at least about 85%, 90%, 95% ormore) of the total iodine species present are in uncomplexed molecularform and contribute to the chemical activity of molecular iodine ascompared to a pure composition of molecular iodine in a 0.1N HClsolution as measured by the potentiometric method of Gottardi (Gottardi,W., Iodine and disinfection: theoretical study on mode of action,efficiency, stability, and analytical aspects in the aqueous system.Arch Pharm, 1999. 332(5): p. 151-157.; Fresenius Z Anal Chem 1983:314;p. 582-5).

The term “thiosulfate titratable iodine” as used herein, refers to alliodine species that can be titrated with sodium thiosulfate includingmolecular iodine, triiodide, hypoiodous acid and polyiodides.

The term “triiodide” refers to a molecule formed by the interaction ofan iodide anion with molecular iodine in an aqueous solution. Thetriiodide species (I₃ ⁻) consists of 3 iodine atoms and has a netnegative charge. Triiodide per se is not a biocide and therefore doesnot directly contribute to biocidal activity in compositions accordingto the present invention.

The term “total iodine” as used herein, refers to the sum of iodineatoms in the following species: iodide, molecular iodine, hypoiodousacid, and all other forms of thiosulfate titratable iodine which arepresent in a composition.

The term “iodate” or “iodate anion” refers to the anion that is theconjugate base of iodic acid wherein an atom of iodine is bonded tothree oxygen atoms. Iodate is represented by the chemical symbol IO₃ ⁻(CAS Registry Number: 15454-31-6).

In the present invention, iodate generates molecular (uncomplexed)iodine within the composition for use as adisinfectant/biocide/antimicrobial pursuant to the present invention. Byrelying on iodate to produce uncomplexed molecular iodine on an ongoingbasis, the concentration of uncomplexed molecular iodine within thepresent composition, remains within a range of concentration whichmaximizes biocidal/germicidal and disinfectant activity for unexpectedlylong periods of time. For example, depending upon the amount of acid andthe buffered pH of the composition (note that a lower pH within therange of the present compositions will tend to result in greaterstability and a more efficient formation of molecular iodine from iodatethan a higher pH), from at least a week to about 5 years, abouttwo-three weeks to about 3-4 years, about a month to about 2-2.5 years,or at least 3-6 months to a year within this range.

The term “molar ratio of molecular iodine to iodate” or vice versarefers to the molar ratio of molecular iodine molecules to iodate anions(or vice versa) in a composition.

The term “ratio of molecular iodine to total iodine” in a substance asused herein, refers to the ratio of the total amount of molecular iodinein a composition of matter divided by the total iodine in the substance.

The term “molar excess of iodate to molecular iodine” in a formulationas used herein refers to refers to the molar ratio of iodate touncomplexed molecular iodine in a composition which is above a 1:1 molarratio.

The term “molar excess of iodate to iodide” or “molar excess of iodate”refers to that increment of a molar ratio of iodate to iodide anion in asolution above a stoichiometric ratio of 1:1; for example, if thestoichiometric ratio is 5 moles of iodate for every 1 moles of iodide,the molar excess of iodate to iodide is 4 in this example. By way offurther example, if the molar ratio is 1.25 to 1 (iodate to iodide), themolar excess of iodate is 0.25. For the purposes of this application, aneffective molar excess of iodate can be achieved by adding iodatedirectly to a composition that contains molecular iodine, e.g. after astoichiometric, ratio of iodide/iodate has reacted to form moleculariodine. In compositions according to the present application, the molarratio of iodate to iodide falls within the range of about

0.1 to about 25, often about 0.25 to about 10 to about 1.25 to 5.0, andabout 1.0 to 7.5 to about 1.25 to 5.0 or about 1.25 to about 5.0 toabout 1.5 to about 5.0 depending upon the final concentration ofuncomplexed (free) molecular iodine desired and the duration ofstability of the composition in providing that concentration of thatuncomplexed molecular iodine.

The term “buffer” or “buffering acid” is used to describe any compatibleinorganic or organic acid which is capable of maintaining a pH ofcompositions according to the present invention within the range ofabout 1.0 to about 6.5, about 1.5 to about 6.5, about 2.0 to about 5.5,about 2.0 to about 5.0, about 1.0 to about 3.5-4.0 with a preferredrange of about 2.0 to about 4.0. The preferred pH of the compositionscontemplated in the current invention will vary based upon the useregimen for an application. If it is necessary or desirable to generatemolecular iodine instantly or in a short time after admixing the activesof this invention the desired pH range if pH 2 to pH 4 with an preferredpH range of pH 2 to pH 3. If a composition will be activated but notused immediately but rather used after a delay, then the preferred pHrange can extend to 6.5. Preferred acids for use in the presentinvention include mono or polyacids which provide a buffering effect tomaintain the pH of compositions according to the present inventionwithin the range of pH, and includes such acidic entities as phosphateacids (including polyphosphate acids), such as phosphoric acid and itsrelated salts sodium dihydrogen phosphate and sodium monohydrogenphosphate, polyphosphoric acid (H_(n+2)P_(n)O_(3n+1)), organic acidshaving from two to 20 or more carbon atoms, including acids according tothe chemical structure R—CO₂H, where R is an optionally substituted(often with one or more hydroxyl groups) C₁-C₂₀ alkyl, alkenyl, alkynyl,aryl or other carbon containing group optionally having more than onedouble bond, preferably C₁-C₁₀ or organic acids or organic acidscontaining more than one carboxylic acid moiety (polycarboxlic acids)such as citric acid, oxalic acid, succinic acid, fumaric acid, malonicacid, maleic acid and various sulphonic acids according to the chemicalstructure R₁—SO₃H, where R₁ is a C₁-C₂₀ alkyl or aryl group which may beoptionally substituted. Organic acids which may be preferred for use inthe present invention include, for example, citric, fumaric, glycolic,lactic, malic, tartaric, acetic, formic, oxalic acid, propanoic,propandioic, butanoic, butanedioic, pentanoic (valeric), pentandioic,hexanoic, hexandioic and benzoic, among others. Other acids which alsomay be used include, for example, acids of bisulfate (sodium, potassiumbisulfate), sulfamic acid, and ethylenediaminetetraacetic acid, amongothers. The use of citric acid, phosphoric acid or other polyacids maybe preferred because of the ability of these acids to accommodate anumber of hydrogen ions in a single chemical entity, which may assist inmaintaining the pH of compositions according to the present inventionwithin a relatively narrow buffered range, thus maintaining activity andstability of the present compositions. A particularly preferred acid,citric acid, refers to the free acid or monobasic (e.g. sodium salt)form of 2-hydroxypropane-1,2,3-tricarboxylic acid acid (CAS RegistryNumber: 77-92-9). Compositions anticipated in the present invention canincorporate the di- and tribasic forms of citric acid provided there isan effective amount of the free acid in order to insure that the pH ofthe compositions lie within a range from about 1.5 to about 6.5, oftenabout 2.0 to 5.5, most often about 2.0 to about 5.0.

The term “activated use-life” as used herein, refers to the length oftime an iodine-based disinfectant/biocidal/antimicrobial productmaintains its initial activated (immediately post activation) level ofthe desired level of thiosulfate titratable iodine when stored underdefined conditions. For instance, the activated use-life for anuncomplexed iodine germicide contemplated in this application may be anhour or a year or more (up to about 5 years) from the time offormulation. The term “stable” as defined herein refers to a compositionaccording to the present invention that can be placed into normaldistribution channels used in commerce which requires a minimumactivated use-life of at least 1 week, or 1 month and preferably atleast 4 to 6 months and most preferably with a activated use-life of 2-5years with no substantial loss of thiosulfate titratable iodine—therebymaintaining activity as a disinfectant/germicide/biocide/antimicrobialcomposition.

The term “combined iodine-based germicide” as defined herein means anuncomplexed iodine germicide in combination with a complementarygermicide or germicides such as peracetic acid, hydrogen peroxide orbenzoyl peroxide alone or in combination with other compatiblegermicidal agents as otherwise described in the present application.

It is noted that used in this specification, the singular forms “a,”“an,” and “the” include plural references unless the context clearlydictates otherwise. Thus, for example, reference to a “source of iodine”includes a single source as well as two or more different sources,reference to an “active” refers to a single as well as to two ordifferent actives, reference to an “inert” includes a single excipientas well as two or more different inerts, and the like.

The term “antimicrobial” refers to the fact that compositions accordingto the present invention often display activity against a broad range ofviruses, bacteria, fungi, spores, mycobacteria, parasites, prions andother microbes.

The term “antiviral” is used to describe compositions according to thepresent invention which display general antiviral activity againstviruses including animal, plant, fungal and bacterial viruses. Viruseswhich may be inhibited and/or eliminated pursuant to the methodsaccording to the present invention using compositions disclosed hereininclude those which impact animals, especially mammals, and inparticular humans, fish, domestic animals and include, for example,papovaviruses, e.g. Polyoma virus and sv40; poxviruses, e.g. Vacciniavirus and variola (smallpox); adenoviruses, e.g., human adenovirus;herpesviruses, e. G. Human herpes simplex types i and ii; parvoviruses,e.g. Adeno associated virus (aav); reoviruses, e.g., rotavirus andreovirus of humans; picornaviruses, e.g. Poliovirus; togaviruses,including the alpha viruses (group a), e.g. Sindbis virus and semlikiforest virus (sfv) and the flaviviruses (group b), e.g. Dengue virus,yellow fever virus and the St. Louis encephalitis virus; retroviruses,e. G. Hiv i and ii, rous sarcoma virus (rsv), and mouse leukemiaviruses; rhabdoviruses, e.g. Vesicular stomatitis virus (vsv) and rabiesvirus; paramyxoviruses, e.g. Mumps virus, measles virus\and sendaivirus; arena viruses, e.g., lassa virus; bunyaviruses, e.g., bunyawere(encephalitis); coronaviruses, e.g. common cold (rhinovirus), GIdistress viruses, orthomyxovirus, e.g., influenza; caliciviruses, e.g.,norwak virus, hepatitis e virus; filoviruses, e.g., ebola virus andmarburg virus; and astroviruses, e.g. Astrovirus, among others.Virtually all viruses are susceptible to compositions according to thepresent invention.

Viruses such as influenza (especially H5N1 influenza), Herpes SimplexVirus (HSV1 and HSV-2), Coxsackie virus, Human immunodeficiency virus (Iand II), Andes virus, Dengue virus, Papilloma, Epstein-Barr virus(mononucleosis), Variola (smallpox) and other pox viruses, West Nilevirus, influenza (H5N1) are relevant targets for antimicrobial action ofcompositions according to the present invention.

A short list of animal viruses that may be relevant targets ofcompositions according to the present invention include:

-   -   Norovirus    -   Reovirus    -   Rotavirus    -   Aphthovirus    -   Parechovirus    -   Erbovirus    -   Kobuvirus    -   Teschovirus    -   Enterovirus    -   Rhinovirus    -   Hepatovirus    -   Hepatitis E virus    -   Rubella virus    -   Lymphocytic choriomeningitis virus    -   HIV-1, HIV-2,    -   HTLV-I    -   Herpes Simplex Virus 1 and 2    -   Cardiovirus    -   Norwalk virus    -   Influenzavirus A, B and C    -   Isavirus,    -   Thogotovirus    -   Coxsackie Virus    -   Dengue virus    -   Yellow fever virus    -   Hepatitis A virus    -   Hepatitis B virus    -   Hepatitis C virus    -   Measles virus    -   Mumps virus    -   Respiratory syncytial virus    -   California encephalitis virus    -   Hantavirus    -   Rabies virus    -   Ebola virus    -   Marburg virus    -   Corona virus    -   Astrovirus    -   Borna disease virus    -   Variola (smallpox virus)

Plant viruses also are relevant targets of compositions according to thepresent invention. The present invention may be used to disinfect,eliminate and/or inhibit the growth of plant viruses, especially incertain agricultural applications, especially including food production.

Plant viruses, which may serve as targets for the present inventioninclude the following:

Partitiviruses, e.g., alphacryptoviruses and betacryptoviruses;Potyviruses, e.g., bymoviruses and ipomoviruses; Bromoviruses, e.g.cucumoviruses and bromoviruses; Comoviruses, e.g. fabiviruses,neopoviruses and comoviruses; Geminiviruses e.g., bigeminivirus,monogeminivirus and bybrigeminivirus; Rhabodoviruses, e.g.,cytorhabdoviruses, nucleorhabdoviruses; Reoviruses, e.g., oryzavirusesand phytoreoviruses; Satellite viruses, e.g., satelliviruses;Tombusviruses, e.g., carmoviruses; Sequiviruses, e.g., sequiviruses andwaikaviruses; among numerous others, including those listed hereinbelow.

Plant Virus Genuses which are targets of the present compositions andmethods, include the following:

-   -   Alfamoviruses: Bromoviridae    -   Alphacryptoviruses: Partitiviridae    -   Badnaviruses    -   Betacryptoviruses: Partitiviridae    -   Bigeminiviruses: Geminiviridae    -   Bromoviruses: Bromoviridae    -   Bymoviruses: Potyviridae    -   Capilloviruses    -   Carlaviruses    -   Carmoviruses: Tombusviridae    -   Caulimoviruses    -   Closteroviruses    -   Comoviruses: Comoviridae    -   Cucumoviruses: Bromoviridae    -   Cytorhabdoviruses: Rhabdoviridae    -   Dianthoviruses    -   Enamoviruses    -   Fabaviruses: Comoviridae    -   Fijiviruses: Reoviridae    -   Furoviruses    -   Hordeiviruses    -   Hybrigeminiviruses: Geminiviridae    -   Idaeoviruses    -   Ilarviruses: Bromoviridae    -   Ipomoviruses: Potyviridae    -   Luteoviruses    -   Machlomoviruses    -   Macluraviruses    -   Marafiviruses    -   Monogeminiviruses: Geminiviridae    -   Nanaviruses    -   Necroviruses    -   Nepoviruses: Comoviridae    -   Nucleorhabdoviruses: Rhabdoviridae    -   Oryzaviruses: Reoviridae    -   Ourmiaviruses    -   Phytoreoviruses: Reoviridae    -   Potexviruses    -   Potyviruses: Potyviridae    -   Rymoviruses: Potyviridae    -   Satellite RNAs    -   Satelliviruses    -   Sequiviruses: Sequiviridae    -   Sobemoviruses    -   Tenuiviruses    -   Tobamoviruses    -   Tobraviruses    -   Tombusviruses: Tombusviridae    -   Tospoviruses: Bunyaviridae    -   Trichoviruses    -   Tymoviruses    -   Umbraviruses    -   Unassigned potyviruses: Potyviridae    -   Unassigned rhabdoviruses: Rhabdoviridae    -   Varicosaviruses    -   Waikaviruses: Sequiviridae    -   Ungrouped viruses

The term “antibacterial” may also be used to describe compositionsaccording to the present invention. Accordingly, the compositionsaccording to the present invention may be used as antibacterial agents.The compositions are useful to eliminate or disinfect numerous types ofbacteria, including gram negative and gram positive bacteria, especiallyincluding drug and multidrug resistant bacteria, including MRSA. A listof bacteria which are targets of the antimicrobial activity ofcompositions according to the present invention include:

Gram positive and gram negative bacteria including cocci and bacilliincluding for example:

Gram Positive:

-   -   Staph aureus;    -   S. epidermidis;    -   S. saphrophyticus;    -   S. haemolyticus;    -   S. hominis;    -   S. capitis S. schleiferi;    -   S. warneri;    -   S. lugdenenis;    -   Strep pyrogenes (gr. A);    -   S. agalactiae (gr. B);    -   E. faecalis;    -   E. faecium;    -   Enterococci;    -   S. pneumoniae;    -   S. mutans group;    -   S. salivarus group;    -   S. sanguis group;    -   S. mitis group;    -   S. angiosus group    -   Abiotrophica defective;    -   A. adiacens;    -   S. milleri;    -   S. bovis;    -   N. gonorrhea;    -   N. meningitides;    -   Moraxella catarrhalis;    -   C. diptheriae;    -   C. jeikenium;    -   C. urealyticum;    -   Lactobacillus sp.;    -   Bacillus anthracia;    -   B. cereus;    -   Listeria monocytogenes;    -   Erisipelothrix rhusiopathiae;    -   Arcanobacterium bemolyticum;    -   Gram Negative;    -   Escherichia coli;    -   Klebsiella pneumoniae;    -   Proteus spp.;    -   Morganella;    -   Providencia;    -   Salmonella enterica;    -   Shigella boydii (serogroup C);    -   S. dysenteriae (serogroup A);    -   S. flexneri;    -   S. sonnei (serogroup D);    -   C. freundii;    -   C. koseri;    -   Enterobacter cloacae;    -   E. aerogenes;    -   S. marcecescens;    -   Vibrio cholera;    -   V. parahaemolyticus;    -   V. vulificans;    -   Aeromonas hydrophila;    -   Plesiomonas shigelloides;    -   Acinetobacter baumannii;    -   A. lowfii;    -   Stenotrophomonas maltophilia;    -   Pseudomonas sp;    -   Pseudomonas aeruginosa;    -   P. fluroescens;    -   P. putida;    -   Burkholderia cepacia;    -   Alkaligenes;    -   Haemophilus;    -   H. influenzae;    -   H. parainfluenzae;    -   H. duceyi;    -   HACEK group;    -   Haemophilus aphrophilus;    -   Actinobacter actinomysetemcomitans;    -   Cariobacter hominis;    -   Eikenella corrodens;    -   Kingella kingii;    -   Bordatella pertussis;    -   Pasteurella multocida;    -   Brucella sp.;    -   Campylobacter;    -   C. jejuni    -   C. coli;    -   C. fetus;    -   Capnocytophaga;    -   Francisella tularensis;    -   Helicobacter pylori;    -   Legionella pneumophila;    -   Mycoplasma pneumoniae;    -   M. hominis;    -   Ureaplasma urealyticum;    -   Bacteroides fragilis group;    -   B. fragilis;    -   B. distansonis;    -   B. thetaiotaomicron;    -   B. uniformis;    -   Proteus vulgaris;    -   B. ovatus;    -   B. uniformis;    -   Bacteroides sp;    -   B ureolyticus    -   Bilophila wadsworthia    -   Porphyromonas species;    -   Prevotella;    -   Fusobacterium;    -   Clostridium sp;    -   C. perfringens;    -   C. botulinum;    -   C. tetani;    -   C. septicum;    -   C. difficile;    -   Actinomyces Israeli;    -   Propionibacterium acnes;    -   Eubacterium;    -   Lactobacillus sp.;    -   Bifidobacterium;    -   Veillonella;    -   Peptostreptococcus;    -   Peptococcus

The compositions according to the present invention may be used asantifungal agents. The compositions are useful to eliminate or disinfectnumerous types of disease causing fungi including Aspergillus,Coccidioides, Histoplasma capsulatum and Candida, especially includingCandida albicans, among others.

The present invention may also be used to inhibit and/or eliminatespores and mold. The term “spores” is used throughout the specificationto describe a unit of asexual reproduction and/or resistance of manyplants, algae, fungi, bacteria and protozoa that are adapted survivaland dispersal of these organisms in unfavorable conditions. Spores areusually unicellular and under favorable conditions can develop into anew organism. Spores may be characterized more specifically assporangiospores from fungi, zygospores from fungi, ascospores fromascomycetes, basidiospores from basidiomycetes, aeciospores, teliosporesand uredeiospores from fungi such as rusts or smuts, oospores fromoomycetes, carpospores and tetraspores from red algae. The term sporesalso includes meiospores, microspores, megaspores, mitospores,zoospores, aplanospores, autospores, ballistospores and statismospores,among others. The present invention may be used to substantially inhibitand/or eliminate spores from numerous surfaces in numerous applicationsas otherwise described herein.

The term “mold” is used to describe a fungus that grows in the form ofmulticellular filaments called hyphae. Molds are a large andtaxonomically diverse number of fungal species where the growth ofhyphae results in discoloration and a fuzzy appearance, especially onfood. Molds are considered to be microbes and do not form a specifictaxonomic or phylogenetic groups, but can found in the divisions ofZygomycota and Ascomycota. Molds often cause biodegradation of naturalmaterials, which can be unwanted when it becomes food spoilage and/ordamage to property. Molds also cause disease in animals and humans oftenresulting from allergic sensitivity to mold spores, from growth ofpathogenic molds within the body, or from the effects of ingested orinhaled toxic compounds (mycotoxins) produced by molds.

There are thousands of known species of molds, which have diverselife-styles including aprotrophs, mesophiles, psychrophiles andthermophiles and a very few opportunistic pathogens of humans. They allrequire moisture for growth and some live in aquatic environments. Likeall fungi, molds derive energy from the organic matter on which theylive, utilizing heterotrophy. Typically, molds secrete hydrolyticenzymes, which degrade complex biopolymers such as starch, cellulose andlignin into simpler substances which can be absorbed. In this way moldsplay a major role in causing decomposition of organic material, enablingthe recycling of nutrients. Molds often grow on stored food for animalsand humans, making the food unpalatable or toxic and are thus a majorsource of food losses and illness. Many prior art strategies (salting,pickling, jams, bottling, freezing, drying) are used to prevent or slowmold growth as well as growth of other microbes. Molds reproduce byproducing large numbers of small spores, which can be inhibited and/oreliminated by the compositions according to the present invention.Common molds include Acremonium, Alternaria, Aspergillus, Cladosporium,Fusarium, Mucor, Penicillium, Rhizopus, Trichoderma and Stachybotrys,among others. The present invention is useful to inhibit and/oreliminate each of these molds from surfaces on or in solutions in whichthey are present.

Prions are another class of important bioagents which may be eliminatedor disinfected using the invention of the present application. Exemplaryprions include Scrapie (Sheep and goats), transmissible minkencephalopathy (TME), chronic wasting disease (CWD) in mule deer andelk, bovine spongiform encephalopathy (BSE) cattle, feline spongiformencephalopathy (FSE) in cats, exotic ungulate encephalopathy (EUE), Kuruin humans, Creutzfeldt-Jakob disease (CJD) in humans, Fatal familialinsomnia (FFI) in humans and Gerstmann-Sträussler-Scheinker syndrome(GSS) in humans.

Parasites are another class of important bioagents which may beeliminated or disinfected using the invention of the presentapplication. Exemplary parasites which are disinfected (eliminated) bycompositions according to the present invention include the following:

-   -   Alveolar Echinococcosis (Echinococcosis, Hydatid Disease)    -   Angiostrongyliasis (Angiostrongylus Infection)    -   Anisakiasis (Anisakis Infection, Pseudoterranova Infection)    -   Ascariasis (Ascaris Infection, Intestinal Roundworms)    -   Babesiosis (Babesia Infection)    -   Balantidiasis (Balantidium Infection)    -   Balamuthia    -   Baylisascariasis (Baylisascaris Infection, Raccoon Roundworm)    -   Blastocystis hominis Infection    -   Cercarial Dermatitis (Swimmer's Itch)    -   Chagas Disease (American Trypanosomiasis)    -   Chilomastix mesnili Infection (Nonpathogenic [Harmless]        Intestinal Protozoa)    -   Clonorchiasis (Clonorchis Infection)    -   Cryptosporidiosis (Cryptosporidium Infection)    -   Cyclosporiasis (Cyclospora Infection)    -   Cysticercosis (Neurocysticercosis)    -   Cystoisospora Infection (Cystoisosporiasis) formerly Isospora        Infection    -   Dientamoeba fragilis Infection    -   Diphyllobothriasis (Diphyllobothrium Infection)    -   Dirofilariasis (Dirofilaria Infection)    -   DPDx    -   Fasciolopsiasis (Fasciolopsis Infection)    -   Foodborne Diseases    -   Kala-azar (Leishmaniasis, Leishmania Infection)    -   Keratitis (Acanthamoeba Infection)    -   Microsporidiosis (Microsporidia Infection)    -   Myiasis    -   Naegleria Infection    -   Neurocysticercosis (Cysticercosis)    -   Neglected Tropical Diseases    -   Opisthorchiasis (Opisthorchis Infection)    -   Paragonimiasis (Paragonimus Infection)    -   Pneumocystis jirovecii Pneumonia    -   Pseudoterranova Infection (Anisakiasis, Anisakis Infection)    -   Sappinia    -   Scabies    -   Soil-transmitted Helminths    -   Strongyloidiasis (Strongyloides Infection)    -   Swimmer's Itch (Cercarial Dermatitis)    -   Taeniasis (Taenia Infection, Tapeworm Infection)    -   Toxoplasmosis (Toxoplasma Infection)    -   Waterborne Diseases    -   Zoonotic Diseases (Diseases spread from animals to people)

In many instances, the compositions according to the present inventionmay be formulated as solutions for application to a surface or forintroduction into a water supply or a swimming pool. In certainembodiments according to the present invention, the composition takesthe form of a cream or lotion to be applied to the skin or othersurface. In such instances, an emulsion is used to formulate thecomposition. The term “emulsion”, “oil-in-water emulsion” and“water-in-oil emulsion” are used synonymously throughout thespecification to describe certain embodiments of compositions accordingto the present invention. An “emulsion” according to the presentinvention is a cream or lotion which is generally formed by thesuspension of a very finely divided liquid, in this case water, inanother liquid, in this case, an oil, or alternatively, an oil, inwater. In the present invention, an emulsion is formed when the waterphase is compatibilized in an oil phase, such that the water phasebecomes dispersed within the oil phase, generally by inclusion of asurfactant or emulsifier. In certain embodiments according to thepresent invention, the composition takes the form of a powder, tablet orpill that will be added to an aqueous and then utilized for a specificuse application. In yet other embodiments the compositions may be orallyingested when configured as a capsule, tablet or powder. In anotherembodiment the composition may be infused subgingivally as a liquid, gelor other medium as a periodontal treatment.

The term “oil” is used throughout the specification to describe any ofvarious lubricious, hydrophobic substances obtained from animal,vegetable and mineral matter which are used in compositions according tothe present invention. Oils for use in the present invention may includepetroleum-based oil derivatives such as purified petrolatum and mineraloil. Petroleum-derived oils include aliphatic or wax-based oils,aromatic or asphalt-based oils and mixed base oils and may includerelatively polar and non-polar oils. “Non-polar” oils are generally oilssuch as petrolatum or mineral oil or its derivatives which arehydrocarbons and are more hydrophobic and lipophilic compared tosynthetic oils, such as esters, which may be referred to as “polar”oils. In addition to the above-described oils, certain essential oilsderived from plants such as volatile liquids derived from flowers, stemsand leaves and other parts of the plant which may include terpenoids andother natural products including triglycerides may also be consideredoils for purposes of the present invention.

Petrolatum (mineral fat, petroleum jelly or mineral jelly) and mineraloil products for use in the present invention may be obtained from avariety of suppliers. These products may range widely in viscosity andother physical and chemical characteristics such as molecular weight andpurity.

Additional oils for use in the present invention may include, forexample, mono-, di- and tri-glycerides which may be natural or synthetic(derived from esterification of glycerol and at least one organic acid,saturated or unsaturated, such as for example, such as acetic,propionic, butyric, caproic, palmitic, stearic, oleic, linoleic orlinolenic acids, among numerous others, preferably a fatty organic acid,comprising between 8 and 26 carbon atoms). Glyceride esters for use inthe present invention include vegetable oils derived chiefly from seedsor nuts and include drying oils, for example, linseed, iticica and tung,among others; semi-drying oils, for example, soybean, sunflower,safflower and cottonseed oil; non-drying oils, for example castor andcoconut oil; and other oils, such as those used in soap, for examplepalm oil. Hydrogenated vegetable oils also may be used in the presentinvention. Animal oils are also contemplated for use as glyceride estersand include, for example, fats such as tallow, lard and stearin andliquid fats, such as fish oils, fish-liver oils and other animal oils,including sperm oil, among numerous others. In addition, a number ofother oils may be used, including C₁₂ to C₃₀ (or higher) fatty esters(other than the glyceride esters, which are described above) or anyother acceptable cosmetic emollient.

Preferred oils for use in the present invention include petrolatum,mineral oil or mixtures of petrolatum and mineral oil where the amountof petrolatum to mineral oil (on a weight/weight basis) ranges fromabout 1:20 to about 10:1, preferably about 1:5 to about 5:1, morepreferably about 1:3 to about 1:1, depending upon the end use of theemulsion composition. The inclusion of petrolatum and/or mineral oiland/or the ratio of petrolatum to mineral oil in the presentcompositions will greatly influence the final viscosity of thewater-in-oil compositions according to the present invention andgenerally, are rather inert to the components which are otherwiseincluded in compositions according to the present invention. Emulsionsaccording to the present invention comprise water in an amount rangingfrom about 25% to about 90%, about 35% to about 85%, about 40% to about80%, about 45% to about 75% by weight and an oil in an amount rangingfrom about 5% to about 65%, about 10% to about 50%, about 15% to about50% and an emulsifier ranging from about 1% to about 15%, about 2% toabout 10%. In addition to the above components, additional componentsmay be added to the emulsion including fragrances, emollients,solvents/diluents, additional antimicrobial agents, pigments, foamingagents, gelling agents, solubilizing agents, humectants, stiffeningagents and mixtures of these components, among numerous othercomponents.

The term “surfactant” is used to describe compositions according to thepresent invention which are included in certain disinfectantcompositions according to the present invention for their ability tosolubilize and remove oils and other materials from a surface exposed tothe present compositions. Preferred surfactants for use in the presentinvention are those surfactants which may produce foams (but are notrequired to) upon exposure to a surface. Exemplary surfactants for usein the present invention include nonionic, anionic, cationic, amphotericand zwitterionic surfactants. Preferred anionic surfactants for use inthe present invention include, for example, alkyl sulfates, alkylethersulfates, alkyl benzene sulfonates, alpha olefin sulfonates, N-alkylsarcosinates, alkyl sulfosuccinates, alkyl phosphates, alkyletherphosphates and alkyl or alkylether carboxylic acid salts, among others.

The term “additional compatible germicide” or “additional germicide” isused to describe compatible germicidal agents which may be furtherincluded in compositions according to the present invention to enhancethe disinfectant/germicidal/antimicrobial activity of compositionsaccording to the present invention. Additional germicidal agents whichmay be included in compositions according to the present inventioninclude, for example, numerous per-oxygen compounds such as peraceticacid, perborate, peroxides, including hydrogen peroxide andbenzoylperoxide, among others, along with alcohols such as ethanol,isopropanol, propanol and saturated octanoic acid. In certainembodiments, caprylic acid may also be included in compositionsaccording to the present invention. The additional germicides are addedto the present compositions to enhance the disinfectant/germicidalproperties of the present compositions and often synergistically enhancethe germicidal activity of compositions according to the presentinvention.

The term “thickening agent”, “gelling agent” or “thickener” is used todescribe a component which may be included in compositions according tothe present invention to increase the viscosity of the composition tomake the composition more readily adhere to a surface, especially aceiling, a vertical surface or a surface which is present on an incline.Gelling agents for use in the present invention include standard gellingagents which are stable to acid solutions and which limit degradationdue to oxidation.

Additional components which can be added to compositions according tothe present invention include components selected from non-aqueoussolvents (ethanol, isopropanol, n-propanol, etc. which also may beincluded as a secondary germicide), surfactants, emulsifiers, includingsecondary emulsifiers, emollients, oils, humectants, oils (polar andnon-polar), conditioning agents, thickeners/thickening agents (includinggelling agents), medicaments, fragrances, preservatives, skin protectingagents, pigments, dyes, coloring agents and mixtures thereof in order toprovide compositions exhibiting characteristics consistent with the useof the compositions, depending upon the surface to be treated, whichsurfaces include biological surfaces especially including keratinous ormucosal tissue of an animal, including a human.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is further described and embellished through thepresentation of the following examples. Accordingly, additionalunderstanding of the present invention, including particular aspects andembodiments, as well as their utility and advantages, will be apparentby referring to the detailed description below. The below describedexamples should not be taken to limit the breadth and application of thepresent invention in any way.

The different biocidal properties of complexed versus uncomplexedmolecular iodine are well known to one skilled in the art. Gottardidemonstrated that the instability of molecular iodine in an aqueousenvironment is due to a complex equilibria established after hydrationof molecular iodine; more than 6 different iodine species are formedincluding iodate (Gottardi, W., Iodine and Iodine Compounds, inDisinfection, Sterilization, and Preservation, S. S. Block, Editor.1991. p. 152-166). Stable aqueous disinfectants based on complexingmolecular iodine were developed in the 1800s and theses formulationsrely upon high concentrations of iodide that serve to complex moleculariodine, e.g. Lugol's solution. Polyvinylpyrrolidone replaced iodide asthe primary complexing agent in iodine-based germicides in the 1950s.

Complexed molecular iodine per se is not biocidal in contrast touncomplexed molecular iodine. This stark distinction in biocidalactivity led to an outbreak of bacterial infections from a batch of 10%PVP-I that harbored viable bacteria (Favero, M. S., Iodine—champagne ina tin cup. Infect Control, 1982. 3(1): p. 30-32). Formulations based oncomplexed iodine are commonly referred to as iodophors and all of thesecompositions contain the vast majority of iodine species in a form thatdo not contribute biocidal activity. In fact, it has been clearlydemonstrated that the biocidal efficacy of an iodine-based germicide isdirectly proportional to the concentration of uncomplexed moleculariodine. (Gottardi, W., Zentralbl Bakteriol [B], 1980. 170(5-6): p.422-30).

The present application teaches compositions and methods that provideuncomplexed formulations of molecular iodine that are stable and capableof being placed into commercial distribution channels. The compositionsdescribed in this application can be formulated to provide the optimalconcentration for a particular use indication in contrast to iodophorcompositions where the concentration of molecular iodine is determinedby the iodophor equilibrium that provides adequate stability formolecular iodine. The compositions anticipated in this application: (a)provide a constant thiosulfate titratable level of iodine over theshelf-life of the product and (b) exhibit a chemical activity ofmolecular iodine that is equal to at least about 50% (often at leastabout 60%) of a pure composition of an equivalent concentration ofmolecular iodine (i.e. equivalent in terms of total iodine) in a 0.1NHCl solution as measured by the potentiometric method of Gottardi. Thecompositions described in this application also provide the ability toincorporate other compatible biocides to enhance the use properties ofmolecular iodine; for example, additional biocides can be selected tocomplement the spectrum of activity or the rate of biocidal activity.The potential benefits of this formulation approach include: use of lessiodine with an associated reduction in environmental burden; lower cost;the ability to provide targeted levels of molecular iodine that areappropriate to different use applications; the ability to incorporateadditional biocidal agents; and a reduced potential for negativeorganoleptic or material incompatibilities.

The compositions and methods taught here include products that are soldready to use and those products which are admixed or diluted by the enduser prior to use. The dosage forms contemplated in this applicationinclude, but are not limited to, solids, pastes, sprays, aerosols,foams, gels, lotions, creams, ointments and liquids. The germicides maybe applied directly to surfaces. Other methods of application include,but are not limited to wipes, rinses, drops, gargles, sprays, hose,dips, towel/towelette, cloth, lavage, injection, irrigation, dip,immersion, sponge, mop, vapor or mist. In preferred aspects of theinvention, the ready-to-use compositions and methods taught hereinprovide an activated use-life of at least 1 month and preferably between6 months and 2 years or even longer (up to about 5 years). During theactivated use-life of the compositions anticipated in this application,the thiosulfate titratable iodine does not decrease substantially belowthe initial concentration and the compositions maintain activity (i.e.they do not become inactive). Maintenance of a minimum concentration forthiosulfate titratable iodine is achieved using three principalformulation strategies: (1) the omission of complexing agents that lowerthe chemical activity of molecular iodine and (2) incorporation of amolar excess of iodate that provides at least a 10% molar excess ofiodate to molecular iodine and as much as a twenty-five-fold molarexcess of iodate to molecular iodine and (3) omission of any additivethat consumes or causes the reduction of molecular iodine to ameasurable degree or that negatively impacts activity.

It is well known to one skilled in the art that the spectrum of activityand speed of kill for different germicidal agents varies. There is apotential benefit of being able to incorporate more than one germicideinto a germicidal composition depending upon which pathogens are ofinterest. The compositions contemplated in this application arecompatible with different germicides provided the additional germicides(1) do not complex molecular iodine (2) do not react with moleculariodine (3) are active at an acid pH and (4) do not reduce the activateduse-life of molecular iodine. Representative additional germicidescompatible with the formulations contemplated in this applicationinclude: hydrogen peroxide; peracetic acid; ethanol; 1-propanol;2-propanol; and saturated octanoic acid.

The compositions contemplated in this application are suitable for useover a temperature range of from below 0 degrees to 58 degreescentigrade. The biocidal activity of uncomplexed molecular iodine ismore rapid than a comparable concentration of complexed molecular iodinesince iodophor compositions lose biocidal activity at low temperaturessince the rate at which complexed molecular iodine dissociates from aniodophor limits the availability of the biocidal form of (moleculariodine).

The pH range for the formulations in this application is between 1.5 and6.5, often 2.0 and 5.5 with a preferred pH range of about 2.0-3.0 to5.0. Commonly used weak organic acids are suitable buffering agents forthe compositions contemplated in this application including citric acid,lactic acid, acetic acid and formic acid, among others disclosed herein;other commonly used buffering agents such as the sodium phosphates arealso compatible with the compositions contemplated in this application.

It is understood that various inert ingredients or additives will beadded to the compositions contemplated in this application includingagents that mask odors, increase solubility for actives or inerts, lowerliquid-to-liquid or liquid-to-solid interfacial tension, controlfoaming, increase viscosity, provide detergency or soil release,chelate, act as a dispersant, lower the vapor pressure of moleculariodine by means other than complexation, reduce scaling, preventflocculation and emulsify. In general, for an additive to be compatiblewith the formulations contemplated in this application said additiveshould (a) not lower the chemical activity (as measuredpotentiometrically) of molecular iodine by more than 5% at the intendeduse concentrations, (b) not affect the stability of molecular iodine asmeasured by sodium thiosulfate titration when the test article is storedat 37 degrees centigrade for 6 weeks and (c) not cause the basecomposition to form a color or present an otherwise unattractiveappearance. It is understood that additives that lower the vaporpressure of molecular iodine by means other than complexation can lowerthe chemical activity of molecular iodine which is acceptable providedthe thiosulfate titratable iodine level is not altered and there is noincrease in the formation of triiodide. For instance, commonly usedsurfactants that are compatible with the formulations contemplated inthis application include C₁₀₋₁₆ sodium dodecyl benzene sulfonic acid,linear alkylbenzenesulfonates, Dowfax akylphenol ethoxylates,gluconamides, nonylphenoxypolyethyleneoxy ethanol sulfate, Ecosurf EH3,Ecosurf EH6, Ecosurf EH9, nonanoic acid 2,3-dihydroxypropyl ester,dodecanoic acid 2,3-dihydroxypropyl ester and capryllic acid and asotherwise described herein.

Applications of the Present Invention

The present invention may be used in the following applications orgeneral uses, among others without limitation as disinfectants,sanitizers, antimicrobial agents and/or biocides:

Low level hard surface disinfectants

Intermediate level hard surface disinfectants

Hospital grade hard surface disinfectant

Sporicides for hard surfaces or medical/dental equipment and instruments

High level disinfectant

Liquid chemical sterilant

Hand sanitizer

Hand wash

Hand rub

Food contact surface sanitizer

Dairy sanitizer

Prevention of food spoilage

Extension of shelf-life for fruits, vegetables, meats, dairy, seafoodand grains

Carcass wash

Poultry dip

Flower vase life extender

Food spoilage retardant

Food sanitizer

Dish and utensil sanitizer (manual and automatic)

Fruit and vegetable cleaner and sanitizer

Meat sanitizer

Fish sanitizer

Grain sanitizer

Vegetable sanitizer

Fruit sanitizer

Water disinfection

Pool disinfection

Aquaculture

Animal husbandry

Agriculture

Oil field biofilm remediation

Seafood processing

Dairy production

Breweries

Meat packing

Pre-procedural rinse (dental office)

Mouthwash

Intra-oral irrigation (for use with oral irrigators such as Water Pik)

Sub-gingival irrigation or infusion (dental office professional use)

Biofilm remediation

Hand scrub (surgical pre-operative)

Antiseptic

Pre-operative patient surgical antiseptic

Ear drops or ear rinse

Eye drops

Contact lens solution

Throat gargle

Throat spray

Oral ingestion for gastrointestinal diseases

Oral ingestion

Wound disinfection

Dialysis equipment disinfection

Vaginal douche

Iodine impregnated medical devices (e.g. catheters and ports)

Iodine impregnated face masks

Iodine impregnated tampons

Iodine impregnated dental floss

Iodine impregnated wound dressings and band-aids

Sinus spray (or rinse)

Nasal spray (or rinse)

Iodine impregnated chewing gum

Iodine impregnated mouth melts

Iodine impregnated lozenges

Iodine toothpaste

Inhalation mist

Inhalers

Vaporizers

Urinary bladder lavage

Abdominal or thoracic cavity lavage

Skin and scalp treatment

Athlete's foot soak

Eyewash

Teat dip

Vaginal cream

Ophthalmic ointment

Colonic irrigation

Environmental mold remediation

Humidifiers

Air conditioning systems

Dental infections

Tissue and organ transplants and grafts

Iodine releasing implants

Disinfecting dental cavity preparations (prior to restoration)

Root canal sealer and irrigant

Egg disinfection

Fish roe disinfection

Condom iodinated lubricant

Oral ingestion for fibrocystic breast disease

Commercial and home dishwashers

Surgical wound closure

Iodine releasing soaps

Government and military use (combating bioterrorism)

Veterinary use

Horticulture

Tattoo parlors

Food handlers

Herpes infections

Periodontal rinse

Trans-tympatic (ear drum) injections for otitis media

Iodine releasing drains

Burn spray

Iodine releasing ear drains (tubes)

Iodine releasing periodontal (subgingival) bioresorbable polymer

Blood dialysis

Iodine impregnated tissues (Kleenex)

Iodine tablets for systemic viral infections

Iodine rectal wipes

Iodine releasing anti-inflammatory (steroidal) ointments and creams

Iodine releasing underarm spray or roll-on deodorants

Iodine impregnated dental fillings

Shampoos

Dental dry socket treatment

Pericoronitis

Female breast nipple infections

Skin graft infections

Dental laboratories

Combined with monoclonal antibodies for viral targeting

Cold and Flu preventive

Dental water lines (biofilm preventive)

Oral Mucositis

EXAMPLES Example 1

The following experiment was performed to demonstrate that a compositionof molecular iodine prepared using a molar ratio of iodide to iodate of5 is not stable in an aqueous environment in the absence ofsequestering/binding agents like polyvinylpyrrolidone. The followingmaterials were used for this example: sodium iodide (Acros Organics,Cat. 203182500; Lot A03011333); sodium iodate (Acros Organics, Cat.201765000 Lot A0322553); sodium carbonate (Fisher Scientific, Cat.5252-3; Lot3AA12080311A) and citric acid (Fisher Scientific, Cat.A940-500; Lot 252559).

Control solutions of molecular iodine were prepared in glass 1 literTeflon-lined screw top bottles. All control solutions contained thefollowing: 0.106 grams of sodium carbonate and 7.5 grams of citric acid.All control solutions were prepared by using a molar ratio of iodide toiodate of 5.0. The concentration of iodide/iodate added to each controlsolution varied depending upon the desired final concentration ofmolecular iodine. The final concentrations of molecular iodine preparedin the stock solutions were: 25 ppm (24.5 mg NaI/6.5 mg NaIO₃), 50 ppm(49 mg NaI/13.3 mg NaIO₃), 75 ppm (74 mg NaI/19.6 mg NaIO₃), 100 ppm (99mg NaI/26.2 mg NaIO₃), 150 ppm (148 mg NaI/39.2 mg NaIO₃) and 250 ppm(208 mg NaI/66.3 mg NaIO₃).

Aliquots of 100 mL were transferred into ten different 150 mLTeflon-lined screw top bottles The bottles were stored at 30 degrees C.in a laboratory in Boynton Beach, Fla. during the summer of 2013. Thefollowing analytical measurements were made on the samples: (1) USPthiosulfate titrations and (2) direct potentiometric measurement ofmolecular iodine.

All free molecular iodine values cited in this example and the otherexamples contained in this application, were determined according to thepotentiometric method (W. Gottardi, 1983, Fresenius Z. Anal Chem.314:582-585). The advantage of the potentiometric method is that theconcentration of free molecular iodine is determined directly insolution without subsequent manipulations, such as extraction orequilibrium dialysis; this provides a more accurate measurement. AFisher reference electrode (Fisher Scientific Company, LLC, Pittsburgh,Pa.; Fisher Catalog No. 13-620-51) and platinum electrode (FisherScientific Company, LLC, Pittsburgh, Pa.; Fisher Catalog No. 1 3-620-115) were used with a Corning Model 345 pH meter (Nova Analytics Corp.,Woburn, Mass.) to make the potentiometric measurements. A cylindricalscrew top bottle lid with two holes drilled through the screw top lidwas used to make potentiometric measurements. The diameter of one holewas sized to fit the iodide ion selective electrode; another hole wassized to fit the platinum electrode. The third hole was drilled to allowreagent to be added to or removed from the bottle via a syringe ifrequired.

A standard stock solution of 0.1N sodium thiosulfate (Acros Organics, 1N, Cat. No.: 124270010) was diluted immediately prior to use and thenused to titrate 1 mL of the test solution after the potentiometricmeasurement was completed. The initial concentrations of the stocksolutions were confirmed with both potentiometric analysis andtitration.

Thiosulfate titration was conducted as follows: (1) calculate how manyμL of a 0.01N sodium thiosulfate was required to titrate 50% of theinitial concentration; (2) add the entire volume of 0.01N sodiumthiosulfate corresponding to 50% of the initial concentration ofmolecular iodine and observe if the solution reaches an endpoint; (3) ifthe sample remains clear for several seconds while stirring then thesample has lost at least 50% of the initial molecular iodineconcentration; (4) if the sample remains blue then the sample is stillconsidered to be stable.

Each day for 49 days a 10 mL sample was withdrawn from two samples ofeach concentration and titrated with thiosulfate as per the standard USPtest. The results were averaged and plotted for each day. For eachconcentration the first measurement that demonstrated a 50% reduction inthiosulfate titratable iodine was identified. For the standard solutionswith initial concentrations of molecular iodine of 100, 150 and 250 ppma 50% loss was observed at day 21 to 24. For the standard solutions withinitial concentrations of molecular iodine of 25, 50 and 75 ppm a 50%loss was observed at day 26 to 29. The concentration of molecular iodinewas measured potentiometrically for each concentration on the first daythat a sample demonstrated a minimum 50% reduction in thiosulfatetitratable iodine. In each instance, the potentiometric measurement offree molecular iodine also demonstrated a minimum 50% loss in freemolecular iodine.

Example 2

The activated use-life for commercial antimicrobial agents is animportant product feature. Some products are stable once activated foryears. A product that exhibits an abbreviated shelf-life is at asubstantial commercial disadvantage. The primary active agent in all ofthe antimicrobial products contemplated in this application is moleculariodine. Prior examples demonstrate that molecular iodine is not stablein an aqueous environment.

It was noticed that a single composition in a series of formulationsexhibited much greater stability than the others even though there wasno chemical basis for this observation since all of the compositionsunder study were intended to contain a stoichiometric ratio of iodate toiodide. It was speculated that a weighing error may have led to thisresults. A simple DOE experiment was conducted to explore thisobservation wherein the weights of the different ingredients were variedhigher and lower than the initially used concentrations. It was observedthat those samples that received a higher concentration of iodate hadenhanced stability. This experiment indicated that the cause of theinitial anomalous result was a higher concentration of iodate. Thissuggested that it is possible to provide a stable minimum level ofthiosulfate titratable iodine in uncomplexed molecular iodineformulations by incorporating iodate in molar excess to moleculariodine.

An experiment was then designed to explore the effect of a molar excessof iodate with respect to extending the aqueous stability of moleculariodine. As previously indicated, if the molar ratio of iodide to iodateof 5 to 1 is used there is a quantitative yield of molecular iodine.i.e. no molar excess. For this experiment the molar ratios of iodide toiodate in the test solutions were: 5.0, 3.32, 2.49, 1.99, 1.66, 1.24 and1.0; these ratios represent the following relative molar excesses ofiodate: to iodide 1.5, 2, 2.5, 3, 4 and 5 fold.

A series of compositions with different iodide to iodate ratios wereprepared as described in experiment 1 using glass 1 liter Teflon-linedscrew top bottles. All of these test solutions initially provided 300ppm of molecular iodine. All solutions contained a 7.5 grams of citricacid. The concentrations of sodium iodate and sodium iodide are shownbelow in Table 1. The solutions were prepared by dissolving the citricacid in 900 mL of distilled water, then under stirring until a clearsolution was formed. Sodium iodide was completely dissolved and then thesodium iodate was added under stirring with the lid on the bottlesealed.

TABLE 1 Iodate to Iodide Molar Excess Molar Excess of Iodate NaI/IO3Ratio Molarity NaI Molarity Iodate — 5.0 0.00197 0.000394 1.5 3.30.00197 0.000591 2 2.5 0.00197 0.000788 2.5 2.0 0.00197 0.000985 3 1.70.00197 0.001182 4 1.2 0.00197 0.001576 5 1.0 0.00197 0.00197

For each formulation, aliquots of 100 mL were transferred into tendifferent 100 mL Teflon-lined screw top bottles. The bottles were storedin at an average temperature of 30 degrees C. in a laboratory in BoyntonBeach, Fla. starting in May of 2013. Every week, a one mL sample waswithdrawn from one of the 100 mL bottles and for each of the differentiodide/iodate ratios a USP thiosulfate titration was performed. A singletransfer of 0.01N sodium thiosulfate which neutralized 240 ppm moleculariodine was added to test solutions. A potentiometric measurement ofmolecular iodine was made at the first time point that reached anendpoint by the single thiosulfate addition.

The control solution which had a molar ratio of 5/1 of iodide to iodatedemonstrated a minimum 20% or greater loss at day 14. The potentiometricmeasurement of the control solution indicated a molar ratio of moleculariodine to thiosulfate titratable iodine of 73.4%. In contrast the samplewith a molar excess of 1.5 of iodate to iodine did not exhibit loss ofthiosulfate titratable iodine over the first 11 weeks. At week 11 themolar ratio of molecular iodine to thiosulfate titratable iodine was76.1%. All test solutions with a molar excess of iodate of 2 or morebeyond the stoichiometric amount did not demonstrate a loss of moleculariodine for 6 months at which point the experiment was terminated. Thisstudy demonstrates that a molar excess of iodate to iodide can maintainthe concentration of molecular iodine for an extended period of time.

Example 3

A variation of the experiment described previously was performed.Instead of using iodide, molecular iodine was weighed and added directlyto the formulation. After the molecular iodine was dissolved, a molarexcess of iodate to molecular iodine was established by adding sodiumiodate at a molar ratio of 1.5, 2.0, 2.5, 3.0, 4.0 and 5.0. The controlfor this experiment did not contain any iodate. The stability ofmolecular iodine was evaluated over time using thiosulfate titration.The thiosulfate titration was conducted as follows: (1) add a volume of0.01N sodium thiosulfate which neutralized 75% of the initialconcentration of molecular iodine and observe if the solution reaches atransient endpoint; 9(2) if the sample clears for a second or two thenthe sample has lost at least 25% of the initial molecular iodineconcentration; (4) if the sample remains blue then the sample is stillconsidered to be stable.

The following materials were used for this example: molecular iodinecrystals (Puritan Products, Bethlehem, Pa.; ACS Reagent Grade, Lot069106); sodium iodate (Acros Organics, Cat. 201765000, Lot A0322553);and citric acid (Fisher Scientific, Cat. A940-500; Lot 252559).

All solutions were prepared by adding 7.5 grams of citric acid to 900 mLof distilled water in a volumetric beaker and the citric acid wasdissolved under stirring. Then, in each solution 0.300 grams ofmolecular iodine was added as crystals and a glass stopper was placed inthe mouth of the volumetric to prevent evaporation; water was added toreach 1 liter and then the molecular iodine was stirred until itdissolved. This solution served as the stock solution for theexperiment.

Varying amounts of sodium iodate were added to 100 mL aliquots of thestock solution in Teflon-lined screw top bottles. The control sample didnot receive any iodide. The number of milligrams of sodium iodate addedto the different experimental samples (100 mL each) was 35.1, 46.7,58.4, 70.1, 93.6 and 117. The iodate was dissolved after screwing thelids tightly shut and placing the bottles on a rocker. The bottles werestored in a laboratory at 30 degrees C. in Boynton Beach, Fla. duringthe summer of 2013. The stability of all of the different samples wasfollowed weekly by USP thiosulfate titrations as described above.

Each week a one mL sample was withdrawn from each of the test solutionsand the control solution and titrated with thiosulfate as describedabove. Any solution that demonstrated a 50% reduction in thiosulfatetitratable iodine was considered to have been unstable. For the standardsolution a 25% loss was observed at the end of the 3^(rd) week. Thesample with a molar excess of iodate to molecular iodine of 1.5 did notdemonstrate a 25% loss until the 12^(th) week. All other samples had notdemonstrated a 25% loss at week 16 which is when the experiment wasended.

Example 4

A further objective was to combine molecular iodine with other agents todemonstrate compatibility of multiple microbicides contemplated in thisapplication. Enhanced microbicidal activity may be obtained by combiningdifferent chemical agents of known germicidal activity in the sameformulation. A 300 ppm molecular iodine composition prepared by reactingiodide and iodate at a 5/1 molar ratio in an acidic solution with amolar excess of iodate to molecular iodine of 2; this composition (thebase composition) was used to determine if other known biocidal agentswould be compatible with this formulation approach.

To determine if a biocide was compatible, the biocide was added atincreasing concentrations to the base solution. If the solution becamedeeply colored the additive was deemed to be incompatible. If the amountof thiosulfate titratable iodine decreased, the solution was deemed tobe incompatible since this indicated that the molecular iodine reactedwith the added biocide or that iodine precipitated due to the biocide'sinterference or interaction with iodine

The following biocides were tested: phenol/phenate; phenolics;orthophenylphenol; benzyl-4-chlorophenol; ethanol; 1-propanol;iso-propanol; parachlorometaxylenol; hydrogen peroxide; sodiumdichloro-s-triazinetrione; amylphenol; phenylphenol;di-isobutyl-phenoxy-ethoxyethyl dimethyl benzyl ammonium chloride; alkyldimethyl benzyl ammonium chloride; alkyl dimethyl ethylbenzyl ammoniumchloride; benzyl-4-chlorophenol;1-octanaminium-N,N-dimethyl-N-octyl-chloride; octanoic acid; diethyltoluamide; N,N″-bis(4-chlorophenyl)-3,12-diimino-2,4,11,13-tetraazatetradecanediimidamide(2:1); 4-chloro-3,5-xylenol; sodium dichloro-s-acid; and peracetic acid.

Most of the additional biocides were not compatible with moleculariodine. The addition of most of the phenolics generated increasinglycolored solutions and also reduced titratable iodine. The quaternaryammonium compounds generally reduced thiosulfate titratable iodine andsome also caused the solution to become colored. Several of thepotential biocides did not reduce thiosulfate titratable iodine for theduration of this experiment which was 6 weeks. These included: hydrogenperoxide (3 to 12%); peracetic acid (25 to 50,000 ppm); ethanol(10-95%); 1-propanol (10-95%); 2-propanol (10-95%); and octanoic acid(saturated).

Example 5

A further objective of this invention was to incorporate surface activeagents in the compositions contemplated in this application to enhancethe cleaning and wetting properties of said compositions. A series ofsurface active agents were screened to insure their compatibility withthe molecular iodine based composition contemplated in this application.A 985 micromolar concentration of molecular iodine was prepared bydissolving elemental iodine crystals in a sealed glass volumetric flaskcontaining the base composition.

The base aqueous composition contained 2.0% n-propanol, 3000 ppmperacetic acid, 4.95% hydrogen peroxide, 1.97 millimolar sodium iodateand 0.5% citric acid. Samples of the following surface active agents orclasses of surface active agents were obtained from variousmanufacturers and evaluated for compatibility with molecular iodine. Fora surface active agent to be compatible it had to (a) not lower theactivity (as measured potentiometrically) of molecular iodine by morethan 5% at the lower and upper suggested use concentrations for saidsurface active agent, (b) not affect the stability of molecular iodineas measured by sodium thiosulfate titration when the test article wasstored at 37 degrees centigrade for 6 weeks and (c) not cause the basecomposition with said surface active agent to form a deep color orotherwise unattractive appearance when the surface active agent wasadded at increasing concentrations.

The following classes (or specific compounds) of surface agent agentswere tested: C₁₀₋₁₆ sodium dodecyl benzene sulfonic acid, linearalkylbenzenesulfonates, lignin sulfonates, fatty alcohol ethoxylates,C₁₂₋₁₃ ethoxylated propoxylated alcohols, polyethoxylatedpolyoxypropylenes, alkylphenol ethoxylates, gluconamides, glyceramides(loss of activity), glyceroglycolipids, nonylphenoxypolyethyleneoxyethanol sulfate, Dowfax, Ecosurf EH3, Ecosurf EH6, Ecosurf EH9, nonanoicacid 2,3-dihydroxypropyl ester, dodecanoic acid 2,3-dihydroxypropylester, capryllic acid and polyvinylpyrrolidone.

Lignin sulfonates, glyceramides (loss of activity), glyceroglycolipidsand polyvinylpyrrolidone exhibited negative properties for theformulations anticipated by this application. These surfactants either(a) reduced thiosulfate titratable within 24 hours at room temperature;(b) immediately reduced the chemical activity of molecular iodine bymore than 10%; or (c) produced a darkly colored solution.

C₁₀₋₁₆ sodium dodecyl benzene sulfonic acid, linearalkylbenzenesulfonates and Dowfax were compatible with the compositionscontemplated under this application provided the concentration used ofthese surface active agents was less than 1.5% (w/w) of the finalcomposition. Akylphenol ethoxylates, gluconamides,nonylphenoxypolyethyleneoxy ethanol sulfate, Ecosurf EH3, Ecosurf EH6,Ecosurf EH9, nonanoic acid 2,3-dihydroxypropyl ester, dodecanoic acid2,3-dihydroxypropyl ester and capryllic acid were compatible at allconcentrations tested.

Microbiological tests (study #130621-204) were initiated on Jul. 2, 2013and completed on Jul. 16, 2013 at BioScience Laboratories located at1765 S. 19th Avenue Bozeman, Mont. 59718. The test article was evaluatedin a spray application versus glass slide carriers contaminated withKlebsiella pneumoniae (ATCC #4352), Staphylococcus aureus (ATCC #6538),and Trichophyton mentagrophytes (ATCC #9533). The test article contained200 ppm of molecular iodine, 3% hydrogen peroxide, 0.2% citric acid, 112mg. monolaurin, 20 ml ethanol, and a molar excess of iodate to moleculariodine of 2.0.

An initial suspension of each challenge species containing approximately10⁸ CFU/mL was prepared; Fetal Bovine Serum was added to each suspensionto produce final challenge suspensions containing a 5% (v/v) soil load.A total of 11 glass slide carriers (microscope slides) were contaminatedwith a 0.01 mL aliquot of each challenge suspension and dried at 35° c.for approximately 35 minutes. Each dried contaminated carrier wastreated with the test solution: the spray bottle containing the testsolution was maintained at a 45° angle and sprayed onto eachcontaminated carrier until the carrier was completely wet.

Each carrier was maintained in a horizontal position and exposed foreither 30 seconds, 1 minute, or 2 minutes (timing of the exposurecommenced upon completion of the spray application). Following theselected exposure time, 10 carriers per challenge species weresubcultured in separate tubes containing a 40 mL neutralizing broth andincubated. Following incubation, the tubes were examined for thepresence of growth, and results were reported as “Growth (+),” or “NoGrowth (−).”

One carrier per challenge species per exposure time was evaluated forviable microbial counts, post-treatment: the treated carrier wastransferred to a tube containing neutralizing solution, and aliquotswere diluted and plated, in duplicate. The plates prepared wereincubated in a manner appropriate for each specific test organism;following incubation, the colonies on the plates were enumerated, andthe viable CFU/carrier was determined.

In addition to the testing of microorganisms which are presented inTables 2 and 3, additional testing of microbes (bacteria or fungus) werealso performed. For the primary bacteria, sixty inoculated carriers(stainless penicylinders) are inoculated with the bacteria and dried.The dried cylinders are then sequentially immersed into 10 ml. of thedisinfectant and exposed to the disinfectant for a predetermined lengthof time. The carriers are transferred to a culture media to neutralizethe disinfectant. The carriers are incubated and examined for thepresence or absence of growth. Other than the primary three bacteria(Tables 2 and 3 hereof), all of the other bacteria are tested on 10carriers.

In the fungicidal test (Trichophyton), the disinfectant is inoculatedwith the fungi in suspension. Exposure is for 5, 10 and 15 minutes. Thefungi is removed and neutralized. The cultures are incubated for thepresence or absence of growth. No growth must be observed after 10minutes of exposure to disinfectant.

In the viral test, the following protocol was used. AOAC use dilutiontest was modified for virus testing as follows: one surface for each oftwo samples, representing two different batches of disinfectant, istested against a recoverable virus endpoint titer of at least 10 viableviral particles from the test surface for the exposure period specifiedon the label at less than or equal to ten minutes.

The results are presented in tables 2-9. In general, the compositionswere essentially effective in eliminating/disinfecting bacteria, spores,fungi and viral titer as set forth in the attached tables. The followingobservations were made for the particular microbes:

Acinetobacter baumannii. This is a serious hospital based infection ofthe infirmed Tested by use dilution method (EPA method for multi-useproducts) must have 0/10 failures to make label claim. The presentinvention passed in 30 sec. Most prior art compositions take minutes.

Candida albicans. This is a serious yeast infection. The presentinvention evidenced 0/10 failures with 30 sec. exposure. Most prior artcompositions take minutes and are less effective.

Klebsiella pneumoniae. This is a highly pathogenic bacterium. It iscausative for pneumonia. Again, the present invention evidenced 0/10failures, with a 30 second kill time. Most prior art products takeminutes and are less effective.

Tricophyton mentagrophytes. This is the causative agent for athletesfoot fungus. Test results complied with EPA criteria and showed 0/10failures with a 30 second kill time. Most products require 5-10 minutes.

Pseudomonas aeruginosa. This is a problematic hospital infection. EPArequires effective disinfection of this organism to qualify as hospitalstrength. EPA testing allows up to 6 failures out of 60 in 10 minutesThe present compositions passed the EPA test with 1 failure in 45seconds.

Salmonella enterica. Same EPA requirements as for Psudeomonas. Thepresent compositions showed only 1 failure out of 60 in 45 seconds,easily surpassing EPA testing criteria of an allowable 10 minutes.

Staph aureus. Another bacteria required by the EPA to establish acomposition as a hospital grade disinfectant. The EPA allows 3 failuresin ten minutes; the present composition showed no failures in 30seconds.

Hepatitis A virus. This is a non-enveloped virus, very difficult tokill. Most products aren't effective against this virus. The presentcompositions totally inactivated this virus in 15 seconds and achieved a4 log kill (compared to 10 minutes allowed by EPA).

Polio virus. This virus is considered the benchmark for virus killingability. Generally, if you kill polio, you can kill any virus. Thepresent composition totally inactivated this virus in 90 seconds with a4 log kill. This kill-time was significantly shorter than the 10 minutesallowed by the EPA.

Norovirus (murine surrogate). The present compositions showed a completeinactivation of this virus in 30 seconds with a 4 log kill. Theallowable EPA kill-time is ten minutes. The results are gleaned from thetables which follow.

TABLE 1 Qualitative Carrier Evaluation-Results Test Formulation preparedwith hard water Challenge Baseline Carrier Number of Suspension RecoveryPositive Initial (CFU/untreated Carriers Challenge Exposure Populationcarrier Post- per Number Microorganism¹ Time (CFU/mL) drying) TestedKlebsiella 30 seconds 3.35 × 10⁸ 2.78 × 10³ 0/10 pneumoniae  1 minute1/10 (ATCC #4352) Staphylococcus 30 seconds 6.65 × 10⁸ 4.42 × 10⁶ 5/10aureus  1 minute 1/10 (ATCC #6538)  2 minutes 0/10 Trichophyton 30seconds 1.87 × 10⁷ 8.60 × 10² 0/10 mentagrophytes  1 minute 0/10 (ATCC#9533)  2 minutes 0/10 ¹Prepared with 5% (v/v) added soil load.

TABLE 2 Quantitative Carrier Evaluation-Results Baseline Post- ChallengeCarrier Exposure Suspension Recovery Carrier Initial (CFU/untreatedRecovery Challenge Exposure Population carrier Post- (CFU/Microorganism¹ Time (CFU/mL) drying) carrier) Klebsiella 30 seconds 3.35× 10⁸ 2.78 × 10³ <4.00 × 10¹ pneumoniae  1 minute <4.00 × 10¹ (ATCC#4352) Staphylococcus 30 seconds 6.65 × 10⁸ 4.42 × 10⁶ <4.00 × 10¹aureus  1 minute <4.00 × 10¹ (ATCC #6538)  2 minutes <4.00 × 10¹Trichophyton 30 econds 1.87 × 10⁷ 8.60 × 10² <4.00 × 10¹ mentagrophytes 1 minute <4.00 × 10¹ (ATCC #9533)  2 minutes <4.00 × 10¹

TABLE 4 Qualitative Carrier Evaluation-Results Test Formulation H (seebelow)^(b) Challenge Baseline Carrier Suspension Recovery^(c) Number ofChallenge Initial (Log₁₀ Positive Microorganism Exposure PopulationCFU/untreated Carriers per (ATCC #)^(a) Application Time (CFU/mL)carrier Post-drying) Number Tested Acinetobacter baumannii Use- 30seconds 1.6550 × 10⁹ 6.3076 0/10 (ATCC #BAA-747) Dilution^(d) Candidaalbicans Use- 30 seconds  3.250 × 10⁸ 3.6766 0/10 (ATCC #10231)Dilution^(d) ^(a)Prepared with 5% (v/v) added soil load ^(b)Testformulation was prepared by mixing the following ingredients in sterileWater-for-Irrigation, USP, to produce 1 liter: 495 mL of 10% hydrogenperoxide, 7.5 grams citric acid, 0.112 grams fatty acid (dissolved in 20mL 70% ethyl alcohol), 9 grams surfactant, 39 mL peracetic acid, and oneVial 2. One 2-liter batch of test formulation was prepared. Resultingformulation was applied via standard Use-Dilution Methodology. ^(c)Threecarriers evaluated: mean log₁₀ recovery reported. ^(d)Reference AOAC955.14.

TABLE 5 Norovirus type 1 Test Formulation #1 Virus: Murine Norovirustype 1 Host Cell Line: RAW Host Cell Line ATCC #TIB-7.1 Volume Platedper Well 1.0 mL Cell Control Dilution Virus Test Neutralization InitialCytotoxicity (Negative (−Log¹⁰) Control 30 sec 1 min 2 min ControlPopulation Control Control) −2 NT CT CT CT NT NT ++++ −3 ++++ 0000 00000000 ++++ ++++ 0000 0000 −4 ++++ 0000 0000 0000 ++++ ++++ 0000 −5 ++++0000 0000 0000 ++++ ++++ NT −6 ++++ 0000 0000 0000 ++++ +++0 NT −7 00000000 0000 0000 0000 0000 NT TCID₅₀ 6.50 ≤2.50 ≤2.50 ≤2.50 6.50 6.25 2.50(log₁₀) Log₁₀ N/A ≥4.00 ≥4.00 ≥4.00 ReductionPercent >99.99% >99.99% >99.99% Reduction + CPE (cytopathic/cytotoxiceffect) present 0 CPE (cytopathic/cytotoxic effect) not detected NT NotTested N/A Not Applicable CT Cytotoxicity Present Note: Data has notbeen QA reviewed

TABLE 6 Poliovirus Test Formulation #1 Virus/Strain: Poliovirus/Chat(ATCC #VR-1562) Host Cell Line: LLC-MK2 Host Cell Line ATCC #CCL-7.1Volume Plated per Well 1.0 mL Cell Control Dilution Virus TestNeutralization Initial Cytotoxicity (Negative (−Log¹⁰) Control 30 sec 1min Control Population Control Control) 0000 −2 NT CT CT NT NT ++++ −3++++ 000+ 0000 NT NT 0000 −4 ++++ 0000 0000 ++++ ++++ 0000 −5 ++++ 00000000 ++++ ++++ NT −6 ++++ 0000 0000 ++++ ++++ NT −7 0000 0000 0000 00++++++ NT −8 0000 NT NT 0000 0000 NT TCID₅₀ 6.50 2.75 2.50 7.00 7.50 2.50(log₁₀) Log₁₀ 3.75 4.00 Reduction Percent 99.98% 99.99% Reduction + CPE(cytopathic/cytotoxic effect) present 0 CPE (cytopathic/cytotoxiceffect) not detected NT Not Tested N/A Not ApplicableConclusion: Poliovirus was completely inactivated by the test product at90 seconds; but not completely inactivated at 60 seconds.

TABLE 7 Hepatitis A Test Formulation #1 Virus/Strain: Hepatitis A Virus(ATCC #VR-1402) Host Cell Line: FRhK-4 Host Cell Line #CCL-1688 VolumePlated per Well 1.0 mL Cell Control Dilution Virus Test NeutralizationInitial Cytotoxicity (Negative (−Log¹⁰) Control 15 sec 30 sec ControlPopulation Control Control) 0000 −2 NT CT CT NT NT ++++ −3 NT 0000 0000NT NT 0000 −4 ++++ 0000 0000 ++++ ++++ 0000 −5 ++++ 0000 0000 ++++ ++++NT −6 ++++ 0000 0000 ++++ ++++ NT −7 0000 0000 0000 0+00 ++0+ NT −8 0000NT NT 0000 0000 NT TCID₅₀ 6.50 2.50 2.50 6.75 7.25 2.50 (log₁₀) Log₁₀4.00 4.00 Reduction Percent 99.99% 99.99% Reduction + CPE(cytopathic/cytotoxic effect) present 0 CPE (cytopathic/cytotoxiceffect) not detected NT Not Tested N/A Not ApplicableA complete inactivation of the virus was shown in testing at 15 secondsand 30 seconds.

TABLE 8 Staph. Aureus Qualitative Carrier Evaluation-Results TestFormulation #1 (see below)^(b) Challenge Baseline Carrier SuspensionRecovery^(c) Number of Challenge Initial (Log10 Positive MicroorganismExposure Population CFU · untreated Carriers per (ATCC #)^(a)Application Time (CFU/mL) carrier Post-drying) Number TestedStaphylococcus Use- 30 4.95 × 10⁸ 6.2851 3/60 aureus Dilution^(d)seconds (ATCC #6538) 60 0/60 seconds 90 0/60 seconds ^(a)Prepared with5% (v/v) added soil load. ^(b)Test Formulation was prepared by mixingthe following ingredients in sterile Water-for-Irrigation, USP, toproduce 1 liter: 495 mL of 10% hydrogen peroxide, 7.5 grams citric acid,0.112 grams fatty acid (dissolved in 20 mL 70% ethyl alcohol), 9 gramssurfactant, 39 mL peracetic acid, and on Vial 2, One 2-liter batch oftest formulation was prepared. Resulting formulation was applied viastandard Use-Dilution Methodology. ^(c)Six carriers evaluated; meanlog₁₀ recovery reported ^(d)Reference AOAC 955.15-Bacterial Use DilutionMethod.

TABLE 9 Pseudomas and Salmonella Qualitative Carrier Evaluation -Results Test Formulation I (see below)^(b) Baseline Carrier Recovery^(c)Number of Challenge (Log₁₀ Positive Challenge Suspension InitialCFU/untreated Carriers Per Microorganism Date of Exposure Populationcarrier Post- Number (ATCC #)^(a) Application Evaluation Time (CFU/mL)drying) Tested seudomonas Use- Jan. 17, 2014 45 seconds 2.69 × 10⁹  5.491/60 aeruginosa Dilution Jan. 24, 2014 1 minute 3.85 × 10⁹  6.96 4/60(ATCC #15442) Salmonella Use- Jan. 17, 2014 45 seconds 1.06 × 10¹⁰ 6.010/60 enterica Dilution Jan. 24, 2014 1 minute 1.17 × 10¹⁰ 7.92^(d) 3/60^(d) serovar Choleraesuis (ATCC #10708) ^(a)Prepared with 5% (v/v)added soil load ^(b)Test formulation was prepared by mixing thefollowing ingredients to produce a 1 liter batch: 737 mL peracetic acid(Peraclean 0.4%), 165 mL hydrogen peroxide (30%), one vial of each ofsodium iodate and sodium iodide, one vial of fatty acid (dissolved in 20mL ethyl alcohol), 7.5 grams citric acid, 9 grams surfactant, and 69grams of sterile Water-for-Irrigation, USP. One 3-liter batch offormulation was prepared on each day of testing. ^(c)Three carriersevaluated: mean log₁₀ recovery reported. ^(d)Challenge species to beretested due to high baseline barrier recoveries.

Example 6—Corrosion

In this example, mild steel and aluminum were exposed to concentrationsof peracetic acid (PAA) ranging from 25-2950 ppm for one week. In allcases, the steel either rusted completely or was severely blackened inone week at 88 deg. F. Aluminum became severely discolored but did notcorrode. Acidified peroxide at 3 & 4.95% rusted steel. Brass becamepitted with 500 ppm PAA. When steel and aluminum were exposed to aformulation, according to this invention, containing 25-2950 ppm PAA, nocorrosion or discoloration was observed on steel after one week. Brassexposed for one week to the same composition resulted in nodiscoloration. In another composition according to the present inventionwith acidified peroxide plus I₂ on steel, no rust was evidenced.

Following the successful result for the present invention, thecomposition was modified such that three ingredients were systematicallyomitted from a formula (which contained peracetic acid as a basecomposition), leaving only one of the components in the composition. Thethree were EH-6, monolaurin and H₂O₂. These compositions were formulatedwith 500 ppm PAA in the formula, but iodine and acid were not present.

Variable Compositions and Results:

-   -   H2O2 only—no corrosion steel    -   EH-6 only (the preferred range of EH-6 in the formula is        0.25-2.0%, optimal range of 0.75-1.0%)—resulted in severe        discoloration, but no rust    -   Monolaurin only—severe discoloration, but no rust.    -   Monolaurin, H₂O₂ and EH removed-severe rust (these experiments        run only on steel).        When mild steel is immersed in a solution of peracetic acid (any        concentration ranging from about 25 to 5000 ppm), it begins to        rust at room temperature in less than 30 minutes. In contrast        the composition of the present invention with the identical        concentration of peracetic acid, does not show any signs of        corrosion, even after one week which is an unexpected result.        Likewise, if you acidify hydrogen peroxide with citric acid, at        the same levels used in the present invention, the steel sample        will rust in hours or days. Moreover, citric acid itself will        result steel without any other components.

Example 7 Food Preservation

An additional embodiment of this invention is the inhibition ofdeterioration or spoilage of foodstuffs. This experiment demonstratesthat compositions of the invention can extend the useful life of variousfoods. The following materials were used for this example: sodium iodide(Acros Organics, Cat. 203182500; Lot A03011333); sodium iodate (AcrosOrganics, Cat. 201765000 Lot A0322553); sodium carbonate (FisherScientific, Cat. S252-3; Lot3AA12080311A) and citric acid (FisherScientific, Cat. A940-500; Lot 252559).

A solution of molecular iodine was prepared in a sterile glass 1 literscrew top bottle that contained 0.5 grams of sodium carbonate, 2.5 gramsof citric acid, 24.5 mg of sodium iodide and 3.25 mg NaIO₃. The finalconcentration of molecular iodine was 25 ppm as determined by the directpotentiometric measurement of molecular iodine.

These experiments were intended to prove the hypothesis thatcompositions of the invention could extend the useful life of variousfoods. These are examples only and by no means limit the variety offoods or the extent to which spoilage is inhibited.

In the testing, the refrigerated shelf life of fruits and vegetables wassignificantly extended and mold formation was prevented compared tocontrols. Testing by an independent laboratory of a food-safecomposition of the present invention confirmed its effectiveness againstfoodborne pathogens, destroying Listeria, E-coli, Salmonella and theNorovirus in 90 sec., achieving over 5 log kill (easily passing the EPArequirement for effectiveness as a food sanitizer). See below. Thisreduction in spoilage also extends to foods such as chicken and othermeats and dairy products and grains among others. Independent laboratorytesting of the present invention on chicken breasts confirmedsignificant pathogen reduction as well as an absence of sensory signs ofspoilage.

In addition, testing with the present invention which contained iodineat lower concentrations (e.g. about 10-50 ppm, preferably about 20-30,often about 25 ppm) can be useful for treating viral and mucosalinfections (including colds, influenza and yeast infections, amongothers). Independent laboratory testing of a safe for human use, 25 ppmiodine formula according to this invention against Rhinovirus andCoronavirus (the viruses most frequently responsible for colds and sorethroats) demonstrated complete inactivation and 4 log kill in 30 sec(see below). These results clearly support the use of the presentinvention for treating oral mucosa, throat and nasal passages to preventor ameliorate colds and sore throats.

Study Results for Development Test RKY01010714.FCAL (A16207) (FelineCalicivirus)

Test Substances: Formula L, Formula I+Ecolab Fruit and Vegetable

Treatment, and Ecolab Fruit and Vegetable Treatment

Test Request Form Number: RKY01010714.FCAL

Project Number: A 16207

Test Substance Preparation: Prepared by Independent Lab

Virus: Feline Calicivirus, Strain F-9 (ATCC VR-782)

Organic Soil Load: 1% fetal bovine serum (FBS)

Exposure Time: 90 seconds

Exposure Temperature: Room temperature (21.0° C.)

Cell Cultures: CRFK (feline kidney cells)

Virus Control Results

Feline Calicivirus=7.25 log₁₀

Cytotoxicity Control Results:

Formula L=Cytotoxicity present at 3.50 log₁₀

Formula L+Ecolab Fruit and Vegetable Treatment=Cytotoxicity present at2.50 log₁₀

Ecolab Fruit and Vegetable Treatment=No cytotoxicity present ≤1.50 log₁₀

The cytotoxicity control is used to determine if the test substance hasany cytotoxic effects on the cell cultures used in the study. Thepercent and log reduction take into account any cytotoxicity observed.

Test Results:

Formula L (Present Invention)

Complete inactivation of the test virus was demonstrated.

A ≥99.98% reduction in viral titer was demonstrated. The log reductionwas ≥3.75 log₁₀.

Formula L+Ecolab Fruit and Vegetable Treatment

Complete inactivation of the test virus was demonstrated.

A ≥99.998% reduction in viral titer was demonstrated. The log reductionwas ≥4.75 log_(in).

Ecolab Fruit and Vegetable Treatment

Complete inactivation of the test virus was not demonstrated.

Test virus was detected at 2.25 log₁₀.

A 99.999% reduction in viral titer was demonstrated. The log reductionwas 5.00 log₁₀.

Study Results for Development Test RKY01010713.TK.3 IA16206) (Listeriamonocytogenes)

Test Substance: Formulation L, Formulation L+Ecolab Fruit and VegetableTreatment,

Ecolab Fruit and Vegetable Treatment

Protocol Number: RKY01010713.TK.3

Project Number: A 16206

Test Substance Preparation: Prepared by ATS Labs

Organism: Listeria monocytogenes (ATCC 19117)

Exposure Time: 90 seconds

Soil: No organic soil load

Actual Exposure Temp: 20.9° C.

Neutralizer: Letheen Broth with 0.07% Lecithin and 0.5% Tween 80

Carrier Population Control Results: 6.1 O log 10

All controls were acceptable.

Test Results:

Formulation L (Present Invention): >99.999% (>5.40 log 10) Reduction at90 seconds

Formulation L+Ecolab Fruit and Vegetable Treatment: >99.999% (>5.40log₁₀) Reduction at 90 seconds.

Ecolab Fruit and Vegetable Treatment: >99.999% (>5.40 log₁₀) Reductionat 90 seconds

Formulation L, Ecolab Fruit and Vegetable Treatment, and FormulationL+Ecolab Fruit and Vegetable Treatment all demonstrated anidentical >99.999% reduction at 90 seconds. All three

test substances had identical 100% kill rates on all test recoveryplates.

Study Results for Development Test RKY01010713.TK.2 (A16205I)(Escherichia coli)

Test Substance: Formulation L, Formulation L+Ecolab Fruit and VegetableTreatment, Ecolab Fruit and Vegetable Treatment

Protocol Number: RKY01010713.TK.2

Project Number: A 16205

Test Substance Preparation: Prepared by ATS Labs

Organism: Escherichia coli (ATCC 11229)

Exposure Time: 90 seconds

Soil: No organic soil load

Actual Exposure Temp: 20.9° C.

Neutralizer: Letheen Broth with 0.07% Lecithin and 0.5% Tween 80

Carrier Population Control Results: 6.33 log 10

All controls were acceptable.

Test Results:

Formulation L (Present invention): >99.999% (>5.63 log 10) Reduction at90 seconds Formulation L+Ecolab Fruit and Vegetable Treatment: >99.999%{>5.63 log 10) Reduction at 90 seconds

Ecolab Fruit and Vegetable Treatment: >99.999% (>5.63 log 10) Reductionat 90 seconds

Formulation L, Ecolab Fruit and Vegetable Treatment, and FormulationL+Ecolab Fruit and Vegetable Treatment all demonstrated anidentical >99.999% reduction at 90 seconds. All three

test substances had identical 100% kill rates on all test recoveryplates.

Study Results for Development Test RKY01010713.TK.1 fA162041 (Salmonellaenterica)

Test Substance: Formulation L, Formulation L+Ecolab Fruit and VegetableTreatment, Ecolab Fruit and Vegetable Treatment

Protocol Number: RKY01010713.TK.1

Project Number: A 16204

Test Substance Preparation: Prepared by ATS Labs

Organism: Salmonella enterica (ATCC 10708)

Exposure Time: 90 seconds

Soil: No organic soil load

Actual Exposure Temp: 20.9° C.

Neutralizer: Letheen Broth with 0.07% Lecithin and 0.5% Tween 80

Carrier Population Control Results: 6.21 log 10

All controls were acceptable.

Test Results:

Formulation L: >99.999% (>5.51 log 10) Reduction at 90 seconds

Formulation L+Ecolab Fruit and Vegetable Treatment: >99.999% (>5.51 log10) Reduction at 90 seconds

Ecolab Fruit and Vegetable Treatment: >99.999% (>5.51 log 10) Reductionat 90 seconds

Formulation L, Ecolab Fruit and Vegetable Treatment, and FormulationL+Ecolab Fruit and Vegetable Treatment all demonstrated anidentical >99.999% reduction at 90 seconds. All three test substanceshad identical 100% kill rates on all test recovery plates.

TABLE 7A Test Product #1 25 pm Virus/Strain: Rhinovirus type 14/1059(ATCC Cat #VR-284) Host Cell Line: MRC-5 Host Cell Line ATCC #CCL-171Dilution Virus Exposure Time Cytotoxicity Neuturalization Cell Control(−Log¹⁰) Control 30 Seconds Control Control (Negative Control) 0000 −2NT CT ++++ NT −3 ++++ 0000 0000 ++++ −4 ++++ 0000 0000 ++++ −5 ++++ 0000NT ++++ −6 ++++ 0000 NT +0++ −7 0000 0000 NT 0000 TCID₅₀ 6.50 2.50 2.506.25 (log₁₀) Log₁₀ N/A 4.00 N/A Reduction Percent 99.99% Reduction + CPE(cytopathic/cytotoxic effect) present 0 CPE (cytopathic/cytotoxiceffect) not detected NT Not Tested N/A Not Applicable CT Cytotoxicity

-   -   Conclusion: The test product #1 of the present invention        completely inactivated Rhinovirus type 14 above the cytotoxicity        level following exposure for 30 seconds.

TABLE 7B Test Product #1 25 pm Virus/Strain: Coronavirus/229E (ATCC Cat#VR-740) Host Cell Line: MRC-5 Host Cell Line ATCC #CCL-171 DilutionVirus Exposure Time Cytotoxicity Neuturalization Cell Control (−Log¹⁰)Control 30 Seconds Control Control (Negative Control) 0000 −2 NT CT ++++NT −3 ++++ 0000 0000 ++++ −4 ++++ 0000 0000 ++++ −5 ++++ 0000 NT ++++ −6++++ 0000 NT +++0 −7 0000 0000 NT 0000 TCID₅₀ 6.75 2.50 2.50 6.25(log₁₀) Log₁₀ N/A 4.25 N/A Reduction Percent 99.99% Reduction + CPE(cytopathic/cytotoxic effect) present 0 CPE (cytopathic/cytotoxiceffect) not detected NT Not Tested N/A Not Applicable CT Cytotoxicity

-   -   Conclusion: The test product #1 of the present invention        completely inactivated Coronavirus strain 229E above the        cytotoxicity level following exposure for 30 seconds.

Further Examples—Food Preservation

Two pints of strawberries were treated with the present invention (asolution) by immersing 1 pint of each of the test articles in 300 mL ofthe 25 ppm solution for 5 minutes. Each of the treated test articles wasallowed to air dry at room temperature and then placed in a refrigeratoralongside the untreated control articles. At the end of one month, bothtreated and untreated samples were evaluated. In each case the untreatedstrawberries were coated with fungi; in contrast, the treatedstrawberries did not exhibit any fungi and appeared fresh with favorableorganoleptic qualities. Furthermore, the treated strawberries exhibitedthe same luster and firm texture as when they were purchased. Theuntreated strawberries were dull in color, less firm and began toshrivel. This experiment is just one example of the large range of foodsthat can be treated with compositions of this application to preventspoilage.

In yet another experiment, mushrooms were immersed in the samecomposition as the strawberries for five minutes and allowed to air drybefore being placed in the refrigerator alongside the untreated control.The untreated mushrooms began to shrivel, exuding liquid. By the end ofone month the untreated mushrooms had lost most of their moisture, hadshrunken significantly in volume and had significantly darkened. Incontrast to this, the treated mushrooms retained their original texture,color and volume.

In still another experiment, blackberries were treated in the samemanner for five minutes as were the strawberries and mushrooms. Thetreated berries and the untreated control berries were thenrefrigerated. Initial signs of mold formation were evident on theuntreated berries within one week. Mold growth continued underrefrigeration until, by the 49^(th) day the untreated berries hadsoftened and were completely overgrown with mold, while the treatedberries exhibited no signs of deterioration or mold growth by day 49when the experiment was terminated.

Example—Spores

The present invention was tested against spores to determine theeffectiveness. The present invention was tested at an independentlaboratory against Bacillus subtilis and Clostridium sporogenes at 50degrees c. and had 0/10 failures on each pathogen, with a 5 min.exposure time according to an EPA protocol. This qualifies the presentinvention as sporicidal. The present compositions are also effectiveagainst spores at room temperature, but exposure is generally for alonger period of time. To inhibit and/or eliminate spores on surfaces orin solution, compositions often are used at a temperature between about5 degrees and 58 degrees Celsius.

The formula used was the same one for all of our standard testing. Thisis significant, since no other intermediate level hospital gradedisinfectant can make such a claim. The present compositions haveefficacy against the same EPA required spores at room temperature,having been evaluated and having demonstrated spore kill at 10 min. onporcelain penicylinders according to an EPA protocol.

The invention claimed is:
 1. An aqueous composition adapted forapplication to keratinous or mucosal tissue of an animal consistingessentially of an antimicrobial effective amount of uncomplexedmolecular iodine (I₂) formed from a source of iodide (I−) in aneffective amount, a source of iodate (IO3−) in an effective amount inmolar excess to said iodine and a predetermined amount of an acid,wherein the resulting molar ratio of molecular iodine to iodate in saidcomposition ranges from 0.1 to 25 to 1.5 to 5.0, the molar ratio ofiodide (I−) to iodate ranges from 1.25 to 5 to 0.1 to 25 and theconcentration of acid in the composition is effective to provide abuffering pH ranging from 1.5 to 6.5, the composition providing a stableconcentration of molecular iodine within the range of 0.5 ppm to 500 ppmfor a period of at least 2 weeks to 2.5 years, said composition furthercomprising an effective amount of at least one additional germicidalagent.
 2. The composition according to claim 1 wherein said molar ratioof iodide (I−) to iodate in said composition ranges from 1.25 to 5 to1.5 to 15.0.
 3. The composition according to claim 1 wherein said molarratio of iodide (I−) to iodate in said composition ranges from 1.25 to 5to 0.5 to 7.5.
 4. The composition according to claim 1 wherein thesource of iodide is selected from the group consisting of sodium iodide,potassium iodide, lithium iodide, calcium iodide, magnesium iodide,hydroiodic acid and mixtures thereof and the source of iodate isselected from the group consisting of sodium iodate, potassium iodate,lithium iodate, calcium iodate, magnesium iodate, hydroiodic acid andmixtures thereof.
 5. The composition according to claim 1 wherein thesource of iodide is sodium iodide, potassium iodide and mixturesthereof, and the source of iodate is sodium iodate, potassium iodate andmixtures thereof.
 6. The composition according to claim 3 wherein thesource of iodide is sodium iodide, potassium iodide and mixturesthereof, and the source of iodate is sodium iodate, potassium iodate andmixtures thereof.
 7. The composition according to claim 1 wherein thesource of iodide is selected from the group consisting of sodium iodide,potassium iodide and mixtures thereof.
 8. The composition according toclaim 1 wherein the source of iodate is selected from the groupconsisting of sodium iodate, potassium iodate and mixtures thereof. 9.The composition according to claim 5 wherein hydroiodic acid is used tocomplement the source of iodide.
 10. The composition according to claim6 wherein hydroiodic acid is used to complement the source of iodide.11. The composition according to claim 1 wherein the concentration ofuncomplexed molecular iodine ranges from 1 ppm to 300 ppm.
 12. Thecomposition according to claim 2 wherein the concentration ofuncomplexed molecular iodine ranges from 1 ppm to 300 ppm.
 13. Thecomposition according to claim 4 wherein the concentration ofuncomplexed molecular iodine ranges from 1 ppm to 300 ppm.
 14. Thecomposition according to claim 4 wherein the concentration ofuncomplexed molecular iodine ranges from 20 ppm to 250 ppm.
 15. Thecomposition according to claim 1 wherein the concentration ofuncomplexed molecular iodine ranges from 10 ppm to 300 ppm.
 16. Thecomposition according to claim 1 further comprising at least one furthercomponent selected from the group consisting of non-aqueous solvents,surfactants, disinfectants, emulsifiers, thickeners/thickening agents,gelling agents suitable for use in the oral cavity, other medicaments,fragrances, preservatives, pigments, dyes, coloring agents and mixturesthereof.
 17. The composition according to claim 1 wherein saidadditional germicidal agent is selected from the group consisting of aperoxide disinfectant, ethanol, isopropanol, propanol, octanoic acid,caprylic acid or a mixture thereof.
 18. The composition according toclaim 16 wherein said additional germicidal agent is selected from thegroup consisting of a peroxide disinfectant, ethanol, isopropanol,propanol, octanoic acid, caprylic acid or a mixture thereof.
 19. Thecomposition according to claim 1 adapted as a mouthwash composition. 20.The composition according to claim 16 adapted as a mouthwashcomposition.